Mast cells (MCs) are mediators of allergy and inflammation and participate in the growth of cancer cells. MCs can promote both neoangiogenesis and tumor growth. They increase in the stroma of certain tumors where they can be recruited by... more
Mast cells (MCs) are mediators of allergy and inflammation and participate in the growth of cancer
cells. MCs can promote both neoangiogenesis and tumor growth. They increase in the stroma of certain
tumors where they can be recruited by tumor-derived chemoattractants, such as monocyte chemotactic
protein-1 (MCP-1), RANTES and stem cell factor (SCF) to selectively secrete inflammatory molecules
including chemical mediators and cytokines (TNF, IL-6 and IL-1). However, MC differentiation pathways
and heterogeneity in cancer are still poorly understood. Human interleukin 1 (IL-1) plays a pivotal role
in the pathogenesis of many diseases and functions, including host response to microbial invasion, injury
inflammatory processes, immunologic challenges and cancer. Inflammation around the tumor includes
the infiltration of mast cells and facilitates cancer growth. MCs are activated by IL-1 which can be
produced by certain cancer cells and stimulate the stromal cells to selectively release IL-6, contributing
to the development of Th-17 cells and increasing inflammation. IL-37, mainly generated by macrophage
cell line, is an IL-1 family member which binds IL-18 receptor α (IL-18Rα) chain, and acts as a natural
inhibitor of immune responses. IL-37 down-regulates cJun induced by IL-1, pro-inflammatory signals
and reduces the expression of the mitogen-activated protein kinase (MAPK) p38α, STAT transcription
factors and p53, affecting cellular differentiation and proliferation. In the present study we report the
relationship between inflammatory mast cells, cancer and the beneficial effect of IL-37.
cells. MCs can promote both neoangiogenesis and tumor growth. They increase in the stroma of certain
tumors where they can be recruited by tumor-derived chemoattractants, such as monocyte chemotactic
protein-1 (MCP-1), RANTES and stem cell factor (SCF) to selectively secrete inflammatory molecules
including chemical mediators and cytokines (TNF, IL-6 and IL-1). However, MC differentiation pathways
and heterogeneity in cancer are still poorly understood. Human interleukin 1 (IL-1) plays a pivotal role
in the pathogenesis of many diseases and functions, including host response to microbial invasion, injury
inflammatory processes, immunologic challenges and cancer. Inflammation around the tumor includes
the infiltration of mast cells and facilitates cancer growth. MCs are activated by IL-1 which can be
produced by certain cancer cells and stimulate the stromal cells to selectively release IL-6, contributing
to the development of Th-17 cells and increasing inflammation. IL-37, mainly generated by macrophage
cell line, is an IL-1 family member which binds IL-18 receptor α (IL-18Rα) chain, and acts as a natural
inhibitor of immune responses. IL-37 down-regulates cJun induced by IL-1, pro-inflammatory signals
and reduces the expression of the mitogen-activated protein kinase (MAPK) p38α, STAT transcription
factors and p53, affecting cellular differentiation and proliferation. In the present study we report the
relationship between inflammatory mast cells, cancer and the beneficial effect of IL-37.
Research Interests:
Multidrug resistance (MDR) to anticancer chemotherapy is often mediated by the overexpression of the plasma membrane drug transporter P-glycoprotein (Pgp) encoded by multidrug resistance gene (MDR1). Various chemosensitizing agents are... more
Multidrug resistance (MDR) to anticancer chemotherapy is often mediated by the overexpression of the plasma membrane drug transporter P-glycoprotein (Pgp) encoded by multidrug resistance gene (MDR1). Various chemosensitizing agents are able to inhibit Pgp activity but their clinical application is limited by their toxicity. Furthermore, hepatotoxicity related to chemotherapy causes delays of treatment in cancer patients and often requires supplementation of anti-tumour therapy with hepatoprotective agents. In this in vitro study, we investigated the effectiveness of an endogenous hepatoprotective agent, S-adenosylmethionine (SAMe), and a natural hepatoprotective compound, Cynarin (Cyn), to inhibit Pgp activity in order to evaluate their potential use as chemosensitizing agents. Human doxorubicin (doxo) resistant uterine sarcoma cells (MES-SA/Dx5) expressing high levels of Pgp were treated with two hepatoprotectors at various concentrations (1, 5 and 10 microM) that are clinically ac...
Research Interests:
Cytokines are involved in the regulation of the immune system and clearly communicate with immune cells and bone cells. Therefore, cytokines are produced by many different cell types and are state. Cytokines such as IL-1, TNF, IL-6,... more
Cytokines are involved in the regulation of the immune system and clearly communicate with immune cells and bone cells. Therefore, cytokines are produced by many different cell types and are state. Cytokines such as IL-1, TNF, IL-6, TGF-b, IL-2, IL-8, M-CSF, IL-12, IL-18 and IFN-, and anti-resorption. The immune system and bone cells require positive and negative regulators to maintain homeostasis. In this article, we discuss the interactions between cytokines and bone cells in maintaining homeostasis of the bone. However, the relationship between intercellular signalling, osteoprogenitor cells, mature osteoblasts, osteocytes and osteoclasts, in regulating the pathophysiology of the bone, still remains to be elucidated. Editorial.
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Endocrinology systems exert an important effect on vascular function and have direct actions on blood vessels. Estrogens provoke an increase in skin elasticity, epidermal hydration, skin thickness, reduce skin wrinkles and augment the... more
Endocrinology systems exert an important effect on vascular function and have direct actions on blood vessels. Estrogens provoke an increase in skin elasticity, epidermal hydration, skin thickness, reduce skin wrinkles and augment the content of collagen and the level of vascularisation. Therefore, there is an intricate cross-talk between skin conditions and stress. In stress, β2-adrenoreceptor (β2AR) pathway, cortisol, epinephrine and norepinephrine increase DNA damage and interfere with the regulation of the cell cycle, contributing to aging and skin diseases. Substance P is a neuropeptide released in the skin from the peripheral nerve and is related to stress and inflammation. SP provokes infiltration of inflammatory cells in the skin and induces a variety of cytokines/chemokines. Corticotropin-releasing hormone (CRH), produced by mast cells, is a neuropeptide also expressed in skin and responds to stress. CRH initiates diverse intracellular signaling pathways, including cAMP, protein kinase C, and mitogen-activated protein kinases (MAPK). Under stress, CRH, glucocorticoids, epinephrine and cytokines are generated. Moreover, the release of ACTH binds the receptor MC2-R and stimulates the generation of glucocorticoids such as corticosterone and cortisol, which interact with the transcription factors AP-1 and NF-kB. In skin keratinocytes, ACTH promotes the generation of pro-inflammatory cytokines, which enhances T-cell activity. Cortisol is immunosuppressive by inhibiting Th1 and Th2 cell response, antigen presentation, antibody and cytokine/chemokine production. However, glucocorticoids are certainly helpful in Th1-mediated autoimmune disorders. On the other hand, cytokines, such as TNF, IL-1 and IL-6, stimulate the generation of CRH and activate HPA axis in inflammatory states. Here, we describe for the first time a cross-talk between endocrinology and skin, including pro-inflammatory cytokines and neurogenic inflammatory pathways.
Research Interests:
Research Interests:
Resveratrol, synthesized in dietary plants and contained in wine, has been reported to play a beneficial role in certain cardiovascular regulatory mechanisms and to inhibit carcinogenesis by activating immune and inflammatory responses... more
Resveratrol, synthesized in dietary plants and contained in wine, has been reported to play a beneficial role in certain cardiovascular regulatory mechanisms and to inhibit carcinogenesis by activating immune and inflammatory responses and apoptosis. The object of this study was to elucidate the "in vitro" effects of different concentrations of resveratrol (10(-4), 10(-5), and 10(-7) M) on human peripheral blood mononuclear cell (PBMC) proliferation and cytokine release. Spontaneous PBMC proliferation was unaffected by resveratrol, while the compound at 10(-4) M inhibited (69%) the PHA-stimulated PBMC proliferation. The proliferation stimulation index (ie, the ratio of PHA-stimulated PBMC proliferation/spontaneous PBMC proliferation) of cultures containing 10(-4) M resveratrol was very low in relation to the control, while the proliferation stimulation index values at 10(-5) and 10(-7) M were similar and slightly higher (without statistical significance), respectively. At ...
Research Interests: Immune response, Cell Division, Concentration, Inflammatory Immune Response, Antioxidants, and 16 moreIn Vitro, Humans, Toxicity, Animals, Male, Statistical Significance, Red Wine, Transcription Factor, Clinical Sciences, Middle Aged, Immune system, Adult, Tumor necrosis factor-alpha, Stilbenes, Cell Proliferation, and Interferon gamma
Vitamin E is found in eight forms in nature which include four tocopherols (alpha, beta, gamma and delta) and four tocotrianols (alpha, beta, gamma and delta). The classic effect of vitamin E is to reduce and prevent oxygen damage to the... more
Vitamin E is found in eight forms in nature which include four tocopherols (alpha, beta, gamma
and delta) and four tocotrianols (alpha, beta, gamma and delta). The classic effect of vitamin E is to
reduce and prevent oxygen damage to the tissue and is useful for the treatment of pain, inflammation
and allergic reactions. In addition to antioxidant activity, vitamin E also has a number of different and
related functions. It protects against cancer, improves immune response, lowers the incidence of infectious
diseases, cardiovascular diseases and is protective in allergy and asthma risk, and other disorders. Vitamin E increases n-6 polyunsaturated fatty acid (PUFA) and decreases n-3 PUFA, an effect that diminishes asthma and allergic diseases. Moreover, vitamin E regulates vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration through its oxidant and non-antioxidant effect. Furthermore, vitamin E modulates the endothelial function by altering VCAM-1-induced oxidative activation of endothelial cell PKCα. However, vitamin E is not consistently associated with asthma and/or allergy, and in some cases there are conflicting results on allergy and inflammatory diseases. The association of vitamin E and allergy appears to be very complex, and further study needs to clarify this dilemma.
and delta) and four tocotrianols (alpha, beta, gamma and delta). The classic effect of vitamin E is to
reduce and prevent oxygen damage to the tissue and is useful for the treatment of pain, inflammation
and allergic reactions. In addition to antioxidant activity, vitamin E also has a number of different and
related functions. It protects against cancer, improves immune response, lowers the incidence of infectious
diseases, cardiovascular diseases and is protective in allergy and asthma risk, and other disorders. Vitamin E increases n-6 polyunsaturated fatty acid (PUFA) and decreases n-3 PUFA, an effect that diminishes asthma and allergic diseases. Moreover, vitamin E regulates vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration through its oxidant and non-antioxidant effect. Furthermore, vitamin E modulates the endothelial function by altering VCAM-1-induced oxidative activation of endothelial cell PKCα. However, vitamin E is not consistently associated with asthma and/or allergy, and in some cases there are conflicting results on allergy and inflammatory diseases. The association of vitamin E and allergy appears to be very complex, and further study needs to clarify this dilemma.
Research Interests:
Microglia derive from mononuclear myeloid progenitors and are a major glial complement of products are implicated in the neuronal destruction usually observed in various neurodegenerative diseases. Microglia cells express corticotropin... more
Microglia derive from mononuclear myeloid progenitors and are a major glial complement of products are implicated in the neuronal destruction usually observed in various neurodegenerative diseases. Microglia cells express corticotropin releasing hormone (CRH) receptors, and activation of microglia by CRH releases bioactive molecules which have a biological effect in the brain and regulate several neurological diseases. CRH plays a pivotal role in stress responses and is a key mediator of the hypothalamic-pituitary-adrenocortical system. CRH is expressed in human mast cells, leading to and act synergistically to increase vascular permeability. CRH also up-regulates IL-18 expression by increasing intracellular reactive oxygen in microglia cells. Here we report the relationship between CRH, microglia and mental disorders.
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Autoimmunity is a disease that occurs when the body tissue is attacked by its own immune system. Multiple sclerosis (MS) is an autoimmune illness which triggers neurological progressive and persistent functions. MS is associated with an... more
Autoimmunity is a disease that occurs when the body tissue is attacked by its own immune system. Multiple sclerosis (MS) is an autoimmune illness which triggers neurological progressive and persistent functions. MS is associated with an abnormal B-cell response and upregulation of T-cell reactivity against a multitude of antigens. Mast cells are the first line of the innate immune system and act by de-granulating and secreting chemical mediators and cytokines. Their participation on the central nervous system has been recognized since the beginning of the last century. They have an important role in autoimmune disease, including MS where they mediate inflammation and demyelinization by presenting myelin antigens to T cells or disrupting the blood–brain barrier and permitting entry of inflammatory cells and cytokines. The participation of mast cells in MS is demonstrated by gene overexpression of chemical mediators and inflammatory cytokines. Here we report the relationship and involvement between mast cells and multiple sclerosis.
Research Interests:
Atherosclerosis is an inflammatory disease and hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Variance in plasma LDL cholesterol concentration may be associated with differences in cardiovascular... more
Atherosclerosis is an inflammatory disease and hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Variance in plasma LDL cholesterol concentration may be associated with differences in cardiovascular disease risk and high levels of lipids are associated with increased risk of developing atherosclerosis. Macrophages, which generate pro-inflammatory cytokines, mainly interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-alpha), are deeply involved in atherosclerosis, as well as mast cells which generate several cytokines, including IL-6 and IFN-gamma, and chemokines such as eotaxin, MCP-1 and RANTES involved in monocyte recruitment and differentiation in the arterial wall. In addition, mast cells participate in lipid retention and vascular cell remodeling, and are mediators of innate and adaptive immunity during atherosclerosis. Mast cells which accumulate in the human arterial intima and adventitia during atherosclerotic plaque progression, release vasoactive and angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid metabolites, histamine, cytokines/chemokines, platelet activating factor (PAF) and proteolytic enzymes. Mast cells can be activated by pro-inflammatory stimuli, including cytokines, hypercholesterolemia, and hyperglycemia, and trigger the endothelial expression of adhesion molecules such as P-selectin, vascular cell adhesion molecule-1 (VCAM-1) and chemokines which mediate the recruitment and adhesion of leukocytes. The participation of mast cells in atherosclerosis is still an enigma and it may be of therapeutic interest to clarify this process.
Research Interests:
Mast cells (MCs) derive from a distinct precursor in the bone marrow and are predominantly found in tissues at the interface between the host and the external environment where they can secrete mediators without overt degranulation. Mast... more
Mast cells (MCs) derive from a distinct precursor in the bone marrow and are predominantly found in tissues at the interface between the host and the external environment where they can secrete mediators without overt degranulation. Mast cells mature under local tissue microenvironmental factors and are
necessary for the development of allergic reactions, through crosslinking of their surface receptors for IgE (FcεRI), leading to degranulation and the release of vasoactive, pro-inflammatory and nociceptive mediators that include histamine, pro-inflammatory and anti-inflammatory cytokines and proteolytic
enzymes. Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demylination within the central nervous system. MCs are involved in the pathogenesis of MS by generating various vasoactive mediators and cytokines and participate in the destruction of the myelin sheath and the
neuronal cells. The process of the development of demyelinating plaques in MS is probably linked with the rupture of the blood–brain barrier by MC products. The effects of natalizumab, which is a very effective drug in reducing the annualized relapse rate and other relapse-based endpoints, are discussed. Here, we report the relationship between MCs and MS.
necessary for the development of allergic reactions, through crosslinking of their surface receptors for IgE (FcεRI), leading to degranulation and the release of vasoactive, pro-inflammatory and nociceptive mediators that include histamine, pro-inflammatory and anti-inflammatory cytokines and proteolytic
enzymes. Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demylination within the central nervous system. MCs are involved in the pathogenesis of MS by generating various vasoactive mediators and cytokines and participate in the destruction of the myelin sheath and the
neuronal cells. The process of the development of demyelinating plaques in MS is probably linked with the rupture of the blood–brain barrier by MC products. The effects of natalizumab, which is a very effective drug in reducing the annualized relapse rate and other relapse-based endpoints, are discussed. Here, we report the relationship between MCs and MS.
Research Interests:
Neuropeptides are involved in neurogenic inflammation where there is vasodilation and plasma protein extravasion in response to this stimulus. Nerve growth factor (NGF), identified by Rita Levi Montalcini, is a neurotrophin family... more
Neuropeptides are involved in neurogenic inflammation where there is vasodilation and plasma protein
extravasion in response to this stimulus. Nerve growth factor (NGF), identified by Rita Levi Montalcini,
is a neurotrophin family compound which is important for survival of nociceptive neurons during
their development. Therefore, NGF is an important neuropeptide which mediates the development
and functions of the central and peripheral nervous system. It also exerts its proinflammatory action,
not only on mast cells but also in B and T cells, neutrophils and eosinophils. Human mast cells can be
activated by neuropeptides to release potent mediators of inflammation, and they are found throughout
the body, especially near blood vessels, epithelial tissue and nerves. Mast cells generate and release NGF
after degranulation and they are involved in iperalgesia, neuroimmune interactions and tissue inflammation.
NGF is also a potent degranulation factor for mast cells in vitro and in vivo, promoting differentiation
and maturation of these cells and their precursor, acting as a co-factor with interleukin-3. In conclusion,
these studies are focused on cross-talk between neuropeptide NGF and inflammatory mast cells.
extravasion in response to this stimulus. Nerve growth factor (NGF), identified by Rita Levi Montalcini,
is a neurotrophin family compound which is important for survival of nociceptive neurons during
their development. Therefore, NGF is an important neuropeptide which mediates the development
and functions of the central and peripheral nervous system. It also exerts its proinflammatory action,
not only on mast cells but also in B and T cells, neutrophils and eosinophils. Human mast cells can be
activated by neuropeptides to release potent mediators of inflammation, and they are found throughout
the body, especially near blood vessels, epithelial tissue and nerves. Mast cells generate and release NGF
after degranulation and they are involved in iperalgesia, neuroimmune interactions and tissue inflammation.
NGF is also a potent degranulation factor for mast cells in vitro and in vivo, promoting differentiation
and maturation of these cells and their precursor, acting as a co-factor with interleukin-3. In conclusion,
these studies are focused on cross-talk between neuropeptide NGF and inflammatory mast cells.
Research Interests:
Inflammation, neurodegeneration, imbalance of neurotransmitter systems, oxidative stress and depression are all risk factors for obesity. There is evidence regarding the cross-talk between adipose tissue and the immune system and obese... more
Inflammation, neurodegeneration, imbalance of neurotransmitter systems, oxidative stress and depression are all risk factors for obesity. There is evidence regarding the cross-talk between adipose tissue and the immune system and obese patients may show an alteration of immune functions with major depression, including immune suppression with reduced T-cell and macrophage activity. Obesity is mediated by inflammatory cells such as lymphocytes, macrophages and mast cells which release pro-inflammatory cytokines and chemokines. Obesity-induced leukocyte infiltrations in adipose tissue cause cytokine/chemokine release and inflammation. Here, we report the relationship between obesity, neurological alterations and inflammation.
Research Interests:
Asthma is a chronic inflammatory disease of the lung and its pathophysiology is initiated by mast cell activation in response to the antigen binding to IgE receptor as well as by TH2 cell activation. Mast cells are well established... more
Asthma is a chronic inflammatory disease of the lung and its pathophysiology is initiated by mast cell activation in response to the antigen binding to IgE receptor as well as by TH2 cell activation. Mast cells are well established effector cells in asthma where they exacerbate the inflammatory response, playing a key role in early phase, degranulating and increasing histamine. Human mast cells possess high affinity IgE receptors and are ubiquitous but predominantly localized in mucosal and connective tissue and are distributed along blood vessels. There are two types of mast cells: connective tissue mast cells (TC) and mucosal mast cells (T mast cells). TC mast cells contain more heparin, whereas T mast cells contain more chondroitin sulfate. In asthma, mast cell activation can trigger degranulation, releasing secretory granule complex and preformed mediators, such as histamine and proteases, along with the synthesis of leukotrines and prostaglandins, and induction of cytokines and chemokines. Leukotrine inhibitors and omalizumab, which inhibits IgE, both relieve the asthma exacerbation when administered to humans and permit to reduce the use of other drugs. The release of cytokines by mast cells, such as TNF-alpha, IL-1, IL-6 and IL-33, participate in the pathogenesis of asthma. Stress worsens asthma, and this effect
is also mediated by mast cell activation through the release of cytokines. Administration of IL-33 in experimental animals provokes pathological effects in the mucosal tissues and augments antibody IgE and IgA in blood vessels. Here, we report the impact of mast cell biology in asthma pathogenesis.
is also mediated by mast cell activation through the release of cytokines. Administration of IL-33 in experimental animals provokes pathological effects in the mucosal tissues and augments antibody IgE and IgA in blood vessels. Here, we report the impact of mast cell biology in asthma pathogenesis.
Research Interests:
IgE is an important marker for allergy and plays a central role in the induction of allergic diseases through its binding of the high affinity receptor on mast cells. Mast cells can influence B cell survival, proliferation and... more
IgE is an important marker for allergy and plays a central role in the induction of allergic diseases through its binding of the high affinity receptor on mast cells. Mast cells can influence B cell survival, proliferation and differentiation into CD138+ cells. Among TH2 cytokines, interleukin (IL)-4 and IL-13
are responsible for class-switching in B cells which resolves in production of allergen-specific IgE antibodies that bind to specific receptor on mast cells. IgE synthesis by B cells is regulated by CD40 ligand, IL-4 and interferon-gamma, therefore inhibition of B cell antigen-specific IgE may prevent the cleavage
of CD23 from B cells, having a therapeutic impact which also includes the removal of circulating free IgE, omalizumab, corticosteroids, mast cell stabilizers, leukotriene receptor antagonist, and others. B cell differentiation into IgE-producing cells requires two signals provided by TH2 cells and IL-4, however IL-4, IL-1 and IL-10 as well as several hormones are critical for the development of TH2 cells, while cytokines, such as interferon (IFN)-alpha, IFN-gamma, IL-12 and transforming growth factor (TGF)-beta play a negative role. However, the exact mechanism of this process has not yet been defined.
are responsible for class-switching in B cells which resolves in production of allergen-specific IgE antibodies that bind to specific receptor on mast cells. IgE synthesis by B cells is regulated by CD40 ligand, IL-4 and interferon-gamma, therefore inhibition of B cell antigen-specific IgE may prevent the cleavage
of CD23 from B cells, having a therapeutic impact which also includes the removal of circulating free IgE, omalizumab, corticosteroids, mast cell stabilizers, leukotriene receptor antagonist, and others. B cell differentiation into IgE-producing cells requires two signals provided by TH2 cells and IL-4, however IL-4, IL-1 and IL-10 as well as several hormones are critical for the development of TH2 cells, while cytokines, such as interferon (IFN)-alpha, IFN-gamma, IL-12 and transforming growth factor (TGF)-beta play a negative role. However, the exact mechanism of this process has not yet been defined.
Research Interests:
Vitamins are natural components of foods and are organic compounds distinct from fat, carbohydrates and proteins. Vitamin A is the generic descriptor for compounds with the qualitative biological activity of retinol. Unlike beta-carotene,... more
Vitamins are natural components of foods and are organic compounds distinct from fat, carbohydrates and proteins. Vitamin A is the generic descriptor for compounds with the qualitative biological activity of retinol. Unlike beta-carotene, vitamin A is not an antioxidant and its benefit is related to possible boosting of immune reactions. The effect of vitamin A on immune function is wide-reaching and its deficiency appears to affect immunity in several ways. Innate and adaptive immune responses are affected in some way by lack of vitamin A. Retinoids seem to act on differentiation of lymphocytes,
antibody production, phagocytosis of macrophages, NK, Treg, and T helper cell activity. In addition, in humans, signs of a vitamin A deficiency also include the dysregulation of cytokine/chemokine generation and release. However, excess of vitamin A has been demonstrated to have toxic effects in most species studied. Here we summarize some important effects of vitamin A in immunity and inflammation.
antibody production, phagocytosis of macrophages, NK, Treg, and T helper cell activity. In addition, in humans, signs of a vitamin A deficiency also include the dysregulation of cytokine/chemokine generation and release. However, excess of vitamin A has been demonstrated to have toxic effects in most species studied. Here we summarize some important effects of vitamin A in immunity and inflammation.
Research Interests:
Serotonin (5-HT) is an important neurotransmitter that acts in both central and peripheral nervous system, and has an impact on cell proliferation, migration and apoptosis. 5HT exerts its effects via several receptors. Treatment with... more
Serotonin (5-HT) is an important neurotransmitter that acts in both central and peripheral nervous system, and has an impact on cell proliferation, migration and apoptosis. 5HT exerts its effects via several receptors. Treatment with anti-5-HT receptors diminish the severity of contact allergy in experimental animals, an effect mediated by mast cells; while an agonist reduces the stress level and relieves pruritus
in patients with atopic dermatitis. Mast cells are important for both innate and adaptive immunity and they are activated by cross-linking of FceRI molecules, which are involved in the binding of multivalent antigens to the attached IgE molecules, resulting in a variety of responses including the immediate release of potent inflammatory mediators. Serotonin is present in murine mucosal mast cells and some authors reported that human mast cells may also contain serotonin, especially in subjects with mastocytosis. Here we report the interrelationship between mast cells, serotonin and its receptor inhibitor.
in patients with atopic dermatitis. Mast cells are important for both innate and adaptive immunity and they are activated by cross-linking of FceRI molecules, which are involved in the binding of multivalent antigens to the attached IgE molecules, resulting in a variety of responses including the immediate release of potent inflammatory mediators. Serotonin is present in murine mucosal mast cells and some authors reported that human mast cells may also contain serotonin, especially in subjects with mastocytosis. Here we report the interrelationship between mast cells, serotonin and its receptor inhibitor.
Research Interests: Inflammation, Mast Cells, Serotonin, Brain, Immunity, and 2 more5-HTP and Anti-Serotonin(5-HTP and Anti-Serotonin)
(5-HTP and Anti-Serotonin)
It is well established that mast cells, which are found in the tissues in the proximity of small blood vessels and post-capillary venules, play a key role in the early phase of IgE-mediated allergic reactions. A greatly expanded... more
It is well established that mast cells, which are found in the tissues in the proximity of small blood vessels and post-capillary venules, play a key role in the early phase of IgE-mediated allergic reactions. A greatly expanded understanding of the biology of IL-3 has emerged since the early 1980s. IL-3 is
a specific factor that stimulates the growth of hematopoietic stem and progenitor cells of a variety of lineages and can promote the proliferation of certain classes of lymphocytes distinct from those that are dependent on IL-2. IL-3 has been identified among the most important cytokines for regulation of
mast cell growth and differentiation, migration and effector function activities of many hematopoietic cells. IL-3 termed multi colony-stimulating-factor (multi-CSF) or mast cell growth factor (MCGF) is a haematopoietic growth factor which stimulates the formation of colonies for erythroid, megakaryocytic,
granulocytic and monocytic lineages. It is predominantly produced by activated T cells, natural killer
(NK) cells and mast cells and supports the growth-promoting effects of SCF on mast cell precursors.
IL-3 causes severe hypersensivity reactions and plays a pivotal role in exacerbating the inflammatory
response in vivo. Here we report the interrelationship between IL-3 and mast cells.
a specific factor that stimulates the growth of hematopoietic stem and progenitor cells of a variety of lineages and can promote the proliferation of certain classes of lymphocytes distinct from those that are dependent on IL-2. IL-3 has been identified among the most important cytokines for regulation of
mast cell growth and differentiation, migration and effector function activities of many hematopoietic cells. IL-3 termed multi colony-stimulating-factor (multi-CSF) or mast cell growth factor (MCGF) is a haematopoietic growth factor which stimulates the formation of colonies for erythroid, megakaryocytic,
granulocytic and monocytic lineages. It is predominantly produced by activated T cells, natural killer
(NK) cells and mast cells and supports the growth-promoting effects of SCF on mast cell precursors.
IL-3 causes severe hypersensivity reactions and plays a pivotal role in exacerbating the inflammatory
response in vivo. Here we report the interrelationship between IL-3 and mast cells.
Research Interests:
Human mast cells (first described in 1879 by Paul Ehrlich) develop from committed precursors in the bone marrow expressing the differentiation marker CD34+ and distinct from the three other myeloid cells. Mast cells are present in various... more
Human mast cells (first described in 1879 by Paul Ehrlich) develop from committed precursors in the bone marrow expressing the differentiation marker CD34+ and distinct from the three other myeloid cells. Mast cells are present in various tissues especially near blood vessels, epithelia and nerves and
they are activated by cross-linking of FcεRI, but also by a number of neuropeptides. NGF mediates a number of inflammatory and autoimmune states in conjunction with an increased accumulation of mast cells which appear to be involved in neuroimmune interactions and tissue inflammation. Here we report some relationships between mast cells and nerve growth factor (NGF).
they are activated by cross-linking of FcεRI, but also by a number of neuropeptides. NGF mediates a number of inflammatory and autoimmune states in conjunction with an increased accumulation of mast cells which appear to be involved in neuroimmune interactions and tissue inflammation. Here we report some relationships between mast cells and nerve growth factor (NGF).
Research Interests:
Vitamin D has a major role in calcium absorption and maintenance of healthy bones. Vitamin D is also involved in cancer, cardiovascular system, allergic diseases, immune regulation and immune disorders. Irradiation of food as well as... more
Vitamin D has a major role in calcium absorption and maintenance of healthy bones. Vitamin D is also involved in cancer, cardiovascular system, allergic diseases, immune regulation and immune disorders. Irradiation of food as well as animals produces vitamin D and more than 90% of previtamin D3 synthesis in the skin occurs in the epidermis. Vitamin D receptor has been found in many cells including T and B lymphocytes, macrophages, mast cells, NK cells and Tregs, and it selectively binds with high affinity to its ligand. Vitamin D binds its receptor VDR, resulting in transcription of a number of genes playing a role in inhibition of MAPK. Its effect may be also mediated by the direct activation of PKC. Vitamin D has the ability to suppress inflammatory cytokines such as TNF, IL-1, IFN-gamma and IL-2; while it increases the generation of anti-inflammatory cytokines IL-4 and IL-10. In B cells, vitamin D3
have also been shown to suppress IgE antibody class switch partly through the inhibition of NF-kB. Here we discuss the relationship between vitamin D, immunity and skin disorders.
have also been shown to suppress IgE antibody class switch partly through the inhibition of NF-kB. Here we discuss the relationship between vitamin D, immunity and skin disorders.
Research Interests:
Inflammatory mediators, such as cytokines, chemokines and arachidonic acid compounds, lead to vascular permeability and dilation and increase sensitization and pain receptors. Proinflammatory cytokines, including tumor necrosis factor,... more
Inflammatory mediators, such as cytokines, chemokines and arachidonic acid compounds, lead to vascular permeability and dilation and increase sensitization and pain receptors. Proinflammatory cytokines, including tumor necrosis factor, are involved in the etiology of clinical neurological
disorders. These cytokines activate nuclear factor-κB (NF-κB) which leads to the activation of different inflammatory genes. TNF implicated in neurological disorders has an important role in the activation of microglia and astrocytes. The inhibition of TNF may lead to the decrease of microglia activation and
can be useful for therapeutic intervention. TNF, at the site of nerve injury may activate mast cells (MCs)
which mediate pathologic events such as headache and pain. TNF is the only cytokine stored in mast cells
and can be rapidly released along with biogenic amines after MC stimulation. Activation of MCs leads to NF-κB and AP1 generation with release of many cytokines including TNF, IL-33 and IL-1. In this paper we discuss the role of TNF in MC activation, mediating pain and neurological disorders.
disorders. These cytokines activate nuclear factor-κB (NF-κB) which leads to the activation of different inflammatory genes. TNF implicated in neurological disorders has an important role in the activation of microglia and astrocytes. The inhibition of TNF may lead to the decrease of microglia activation and
can be useful for therapeutic intervention. TNF, at the site of nerve injury may activate mast cells (MCs)
which mediate pathologic events such as headache and pain. TNF is the only cytokine stored in mast cells
and can be rapidly released along with biogenic amines after MC stimulation. Activation of MCs leads to NF-κB and AP1 generation with release of many cytokines including TNF, IL-33 and IL-1. In this paper we discuss the role of TNF in MC activation, mediating pain and neurological disorders.
Research Interests:
Vitamin B1 (thiamin) is considered to be the oldest vitamin and in 1936 R.R. Williams and colleagues determined its chemical structure and were able to synthesize this vitamin. Vitamin B1 influencespro-apoptotic proteins, mitochondrial... more
Vitamin B1 (thiamin) is considered to be the oldest vitamin and in 1936 R.R. Williams and colleagues determined its chemical structure and were able to synthesize this vitamin. Vitamin B1 influencespro-apoptotic proteins, mitochondrial membrane potential, cytochrome C release, protein kinases, p38-MAPK, suppresses oxidative stress-induced NF-kappaB and has anti-inflammatory properties. Deficiency of vitamin B1 may cause beriberi, dysfunction of the nervous system, neuroinflammation, T cell infiltration, chemokine CCL2 activation, over expression of proinflammatory cytokines, such as IL-1, TNF, IL-6, and arachidonic acid products, and induces expression of CD40 by the microglia and CD40L by astrocytes which provoke the death of neurons. Here we report the relationship between vitamin B complex and immunity.
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Acute bronchiolitis is the most common lower respiratory tract infection in young children and may be life-threatening in those with underlying cardiac or respiratory conditions. We evaluated the nasal and serum levels of human neutrophil... more
Acute bronchiolitis is the most common lower respiratory tract infection in young children and may be life-threatening in those with underlying cardiac or respiratory conditions. We evaluated the nasal and serum levels of human neutrophil elastase (HNE) in patients with acute respiratory syncytial virus (RSV) bronchiolitis and investigated the correlation of these levels with illness severity. Fifty-one patients (28 boys,
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Spontaneous bacterial peritonitis (SBP) occurs as a direct consequence of bacteria entering ascitic fluid (AF) from the intestinal lumen trough in several ways, including the hematogenous and mesenteric lymph nodes route. There are few... more
Spontaneous bacterial peritonitis (SBP) occurs as a direct consequence of bacteria entering ascitic fluid (AF) from the intestinal lumen trough in several ways, including the hematogenous and mesenteric lymph nodes route. There are few studies on the cytokine profile of ascitic-derived mononuclear cells of patients with SBP, particularly on granzyme B (GZB). The aim of the present study was to verify whether patients with SBP have GZB-positive cells, whether they are increased in patients with aseptic ascites, and their trend after antibiotic treatment. We enrolled 36 consecutive patients (24 males and 12 females) with SBP on histologically-proven hepatitis C virus cirrhosis (group A) and 20 patients (11 males and nine females with ascites, but without evidences of SBP (group B). The diagnosis of SBP was made according to the following criteria: positive colture in AF or blood (at least two cultures) and neutrophils in AF (>250 mL polymorphonuclear leukocytes). For these patients we used ELISpot to assay GZB production on purified mononuclear cells in ascitesand peripheral blood, coupled with tumor necrosis factor-alpha tested using ELISA. A non-parametric statistical analysis was used to assess significant differences and correlations. We found positive culture in all of the patients with SBP (80% Escherichia coli; 20% Enterococcus faecium). Furthermore, the patients in group A had a higher number of GZB spot-forming colonies than the patients in group B (P < 0.001). GZB-positive cells were lower in the peripheral blood than those found in the AF of patients with SBP, while no differences were found between blood and AF in group B. Furthermore, after antibiotic treatment, GZB was reduced in the patients with SBP (P < 0.05). In conclusion, GZB may be an important mediator of the immune response towards bacteria in AF and could be used as a diagnostic tool.
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T-cell immunoregulatory cytokines influence the persistence of hepatitis C virus (HCV) chronic infection and the extent of liver damage. Th1 cytokines positively correlate with hepatic inflammation in chronic hepatitis B virus (HBV)... more
T-cell immunoregulatory cytokines influence the persistence of hepatitis C virus (HCV) chronic infection and the extent of liver damage. Th1 cytokines positively correlate with hepatic inflammation in chronic hepatitis B virus (HBV) infection. The pro-inflammatory, cytokines IL-6 and IL-18, are involved in viral clearance and in metabolic and viral hepatic diseases, respectively. The aim of this study was to evaluate the profile of Th1/Th2 cytokines in HCV and HBV hepatitis. HBV-infected patients showed higher plasma IFN-gamma levels than the HCV+ patients or the control group (p <0.0001). Plasma TNF-alpha and IL-2 were higher in HBV+ in comparison to HCV+ patients (p <0.001) or the control group (p <0.005). Plasma IL-6 and IL-18 were higher in both groups of patients compared to the control group (p <0.04). In HCV+ and HBV+ groups, IL-6 was positively correlated with the duration of the illness (p <0.01 and <0.001, respectively) and viral load (p <0.001 and <...
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HIV-related metabolic abnormalities include hypertriglyceridemia, hypercholesterolemia, insulin resistance, and diabetes mellitus. Recent studies suggest a role of ghrelin in promoting the deposition of triglycerides (TG) in the liver and... more
HIV-related metabolic abnormalities include hypertriglyceridemia, hypercholesterolemia, insulin resistance, and diabetes mellitus. Recent studies suggest a role of ghrelin in promoting the deposition of triglycerides (TG) in the liver and regulating the metabolic action of adiponectin. Visceral fat is a key regulator of inflammation and it secretes proinflammatory cytokines (eg, interleukin-18, IL-18), with potential atherogenic activity. The aim of this study was to assay serum concentrations of ghrelin, adiponectin, and IL-18 in HIV+ patients, with and without hypertriglyceridemia, who were receiving highly active antiretroviral therapy (HAART). The 49 HIV+ patients were divided in 2 groups: 17 patients with serum TG concentration >200 mg/dl (group A) and 32 patients with normal serum TG concentration (group B). All subjects underwent viral and immunological evaluations and determinations of serum cholesterol, glucose, ghrelin, adiponectin, and IL-18. No differences of viral an...
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MCP-1 is a small (8-10 KDa) protein and a prototype member of the CC chemokine ß subfamily, which plays a critical role in acute and chronic inflammation. Recent evidence suggests an important role for MCP-1, MCP-2 and MCP-3 in a number... more
MCP-1 is a small (8-10 KDa) protein and a prototype member of the CC chemokine ß subfamily, which plays a critical role in acute and chronic inflammation. Recent evidence suggests an important role for MCP-1, MCP-2 and MCP-3 in a number of pathological states, including delayed type hypersensitivity conditions, parasitic infections and rheumatoid arthritis. Forty BALB-c mice were treated with
Research Interests: Skeletal muscle biology, Inflammation, Rheumatoid Arthritis, Molecular and cellular biology, Mice, and 11 moreAnimals, Male, Time Factors, Tumor necrosis factor-alpha, Chronic Inflammation, Tumor Necrosis Factor–α (TNF), Molecular and Cellular Biochemistry, Trichinellosis, Monocyte Chemotactic Protein-1, Biochemistry and cell biology, and Gene Expression Regulation
Interleukin (IL) 6 is a pleiotropic cytokine (26 kDa) that originally was named interferon beta 2 or B cell-stimulating factor or differentiating B cell factor inducing immunoglobulin production. IL-6 is produced in many diseases. After... more
Interleukin (IL) 6 is a pleiotropic cytokine (26 kDa) that originally was named interferon beta 2 or B cell-stimulating factor or differentiating B cell factor inducing immunoglobulin production. IL-6 is produced in many diseases. After secretion, IL-6 binds to its receptor IL-6R alpha (gp 80), the IL-6R alpha complex then recruits the signal-transducing beta-subunit (gp 130), which is the functional complex for signal transduction. In addition, activation of Th2 cells or mast cells also produce IL-6, which mediates immune responses, inflammation, acute phase responses, hematopoiesis, cancer, inflammatory bowel disease, etc. IL-6 also is a crucial cytokine for mast cell maturation. Human cord blood CD34+ cells differentiate and grow into mast cells in the presence of stem cell factor (SCF) and IL-6, causing increases in cell size, frequency of chymase positive cells, and intracellular histamine levels when compared with cells treated with SCF alone. Activated mast cells increase IL-...
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Monocyte chemotactic protein-1 (MCP-1) and MCP-3, the most active and representative compounds of the CC chemokine family, are proinflammatory cytokines that attract and activate specific types of leucocytes. We have used highly purified... more
Monocyte chemotactic protein-1 (MCP-1) and MCP-3, the most active and representative compounds of the CC chemokine family, are proinflammatory cytokines that attract and activate specific types of leucocytes. We have used highly purified isolated rat peritoneal mast cells (RPMC) cultured for different lengths of time with and without MCP-1 (200, 100, 50 and 25 nM). Our data clearly show that MCP-1 (200 nM) causes a marked release of [3H]serotonin ([3H]5HT and histamine, which reach a peak at 40 min of incubation (56.6 +/- 5.3 and 34.7 +/- 6 above the control, respectively). In dose-response experiments, MCP-1 (200, 100, 50, 25, 12.5, 6.25 and 3.12 nM) provoked a dose-dependent release of [3H]5HT and histamine from RPMC, which was maximum at 200 nM. After preparation of the histidine decarboxylase (HDC) probe, a Northern blot analysis was determined for HDC mRNA. After 4 hr, steady-state levels of HDC mRNA were induced in a dose-dependent manner by MCP-1 (200-25 nM), compared to the ...
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To investigate the association between plasma interleukin-18 (IL-18) levels and atherosclerosis in patients with obstructive obstructive sleep apnea hypopnea syndrome (OSAHS). Based on apnea hypopnea index (AHI) during sleep monitored by... more
To investigate the association between plasma interleukin-18 (IL-18) levels and atherosclerosis in patients with obstructive obstructive sleep apnea hypopnea syndrome (OSAHS). Based on apnea hypopnea index (AHI) during sleep monitored by polysomnography, 52 male patients with OSAHS were recruited and divided into a mild OSAHS group (n = 16), a moderate group (n = 18), and a severe group (n = 18). Eighteen healthy subjects were selected as the control group. Twenty patients with moderate-to-severe OSAHS underwent continuous positive airway pressure (CPAP) treatment. HDL5000 color Doppler ultrasound was used to measure intima-media thickness (IMT) of the jugular arteries. Plasma IL-18 levels were measured by ELISA. Analysis of variance, paired-samples T test and Pearson correlation analysis were used for statistics. Compared with the plasma IL-18 levels in the control group [(250 +/- 76) ng/L], there was a significant increase in the mild OSAHS group [(352 +/- 76) ng/L], moderate grou...
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Hypoxia is a potent regulator of various biological process. Mammalian cells respond to hypoxia by increased expression of several genes. The aim of this study was to evaluate the effects of chronic exposure to low oxygen tension on the... more
Hypoxia is a potent regulator of various biological process. Mammalian cells respond to hypoxia by increased expression of several genes. The aim of this study was to evaluate the effects of chronic exposure to low oxygen tension on the induction of inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) in rat heart. Male Wistar rats were assigned randomly to 4 groups: (A) control rats maintained in normoxic conditions for 7 and 14 days; (B) rats maintained in hypoxic conditions for 7 and 14 days; (C) rats maintained in normoxic conditions for 7 days and then transferred to hypoxic conditions for 7 days; and (D) rats maintained in hypoxic conditions for 7 days and then transferred to normoxic conditions for 7 days. In Group A, iNOS and HO-1 immunoreactivities were not evident; in Group B these immunoreactivities increased from day 7 to 14; in Group C the immunoreactivities decreased on day 7, compared to day 14; and in Group D, the immunoreactivities increased on day 7, ...
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Exposure to aluminum has been reported to lead to neurotoxicity. Mitochondria are important organelles involved in maintaining cell function. This study investigates the effect of aluminum on mitochondria in rat neural cells. The... more
Exposure to aluminum has been reported to lead to neurotoxicity. Mitochondria are important organelles involved in maintaining cell function. This study investigates the effect of aluminum on mitochondria in rat neural cells. The ultrastructure of mitochondria was observed, and the cell death rate (CDR), reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and 3-[4,5demethyl-2-thiazalyl]-2,-5diphenyl-2H-tetrazolium bromide (MTT) were measured to investigate the effect of aluminum on the mitochondrial structure and its function in neural cells. Results observed from the mitochondrial ultrastructure show that aluminum may impair the mitochondrial membrane and cristae. Increased CDR, enhanced ROS, decreased MMP, and decreased enzyme activity in mitochondria were observed in the Al-exposed neurons (100 500 microM). The present study demonstrates that alteration in the mitochondrial structure and function plays an important role in neurotoxic mechanisms induced by aluminum.
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IL-1 is a mediator of the acute inflammatory response and plays a key role in influencing growth and differentiation of immunocompetent lymphocytes. It can enhance transcription and secretion of the T-cell growth factor interleukin-2... more
IL-1 is a mediator of the acute inflammatory response and plays a key role in influencing growth and differentiation of immunocompetent lymphocytes. It can enhance transcription and secretion of the T-cell growth factor interleukin-2 (IL-2) and can stimulate the expression of membrane receptors for IL-2. However, the regulation and control of IL-1 activities are poorly understood. Recently an IL-1 inhibitor, interleukin-1 receptor antagonist (IL-1ra), has been described and cloned. This protein is a monokine originally found in the urine of febrile patients and in supernatants of human monocytes adhering to an IgG-coated surface, with an approximate molecular weight of 17 kDa, which is similar to IL-1 beta but having no IL-1-like activity and antagonizing IL-1 by binding to its cell surface receptor. These studies have examined some biological properties of hrIL-1ra, such as its effects on the secretion of IL-1 alpha or IL-1 beta and IL-2, the surface expression of IL-2R and DNA synthesis by peripheral blood mononuclear cells (PBMC). PBMC from normal volunteers were separated and used at a concentration of 2.5 x 10(6) cells/ml. The cells were pretreated for 2 h with hrIL-1ra (0.025-250 ng/ml), treated with LPS (10 ng/ml), and IL-1 alpha and IL-1 beta secretion were determined by an ELISA method. In addition the influence of hrIL-1ra (25 ng/ml) on IL-2 generation was determined. In another set of experiments, flow cytometric analysis with an anti-CD25 monoclonal antibody was determined on PHA-stimulated PBMC pretreated with hrIL-1ra (2 h) and cultured for 48 h. The inhibition by hrIL-1ra of IL-2R expression was dose-dependent and when hrIL-1ra was used at 250 ng/ml the IL-2R was completely abolished. Lymphocyte DNA synthesis calculated from the net uptake of [3H]-thymidine (3H-TdR) was also inhibited by hrIL-1ra (0.025-25 ng/ml). In this report we found that hrIL-1ra inhibits, in a dose-dependent manner, the secretion of IL-1 alpha, IL-1 beta, IL-2, the surface expression of IL-2R and 3H-TdR incorporation in PBMC in vitro. These data suggest a new biological activity of hrIL-1ra and further extend the immunomodulatory potential and significance of this new cytokine. The action of IL-1ra on modulating the synthesis of IL-1 may be of paramount importance in the regulation of these effects.
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Allergy is the result of a complex immune cascade leading to the disregulated production of Th2 cytokines, the generation of allergen-specific IgE-producing B cells and the subsequent activation and degranulation of mast cells upon... more
Allergy is the result of a complex immune cascade leading to the disregulated production of Th2 cytokines, the generation of allergen-specific IgE-producing B cells and the subsequent activation and degranulation of mast cells upon allergen challenge. Mast cell effector function significantly influences the quantity, duration and magnitude of most allergic reactions. Here, using isolated human umbilical cord blood mast cells (HUCBMC) from CD34+ cells, activated with anti-IgE (10 microg/ml) in culture, we found an augmented release of IL-6, tryptase and histamine (p &lt; 0.01 compared with control). In addition, in these cells anti-IgE (10 microg/ml) activated the expression of histidine decarboxylase (HDC) and IL-6. In these studies we describe a new biological activity of anti-IgE in inducing histidine decarboxylase and IL-6, suggesting that this cytokine may have an important effect on allergic and inflammatory diseases mediated by mast cells. Moreover, with these data we confirm the immunoregulatory and inflammatory function of mast cells.
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The activation of monocytes/macrophages by several stimuli is an initial event in the inflammatory response. To ascertain the importance of LTB(4) and 5-lypoxigenase in the inflammatory site, we isolated and stimulated rat adherent... more
The activation of monocytes/macrophages by several stimuli is an initial event in the inflammatory response. To ascertain the importance of LTB(4) and 5-lypoxigenase in the inflammatory site, we isolated and stimulated rat adherent granuloma macrophages (RAGMs) with calcium ionophore in the presence or absence of regulated on activation, normal T expressed and secreted (RANTES) [CCL5] at different concentrations. We tested the hypothesis that RANTES may influence the production of LTB(4) stimulated by calcium ionophore A23187 (2.5 microM/ml) in rat adherent granuloma macrophages derived from granuloma induced by potassium permanganate diluted 1:40 saturated solution. To test this hypothesis, we measured LTB(4) production, in rat granuloma macrophages stimulated with A23187 (2.5 microM) alone and in combination with RANTES at different concentrations. In these studies, the cell-free supernatant of stimulated RAGMs with the ionophore A23187, resulted in a drastic increase of LTB(4). However, when the cells were treated with the combination RANTES plus A23187 the stimulatory effect was more pronounced than A23187 alone. LTB(4) production was quantitated. The calcium ionophore A23187 directly induced LTB(4) in macrophages, this production was markedly enhanced when the cells were pretreated with RANTES. However, the addition of RANTES in the absence of calcium ionophore A23187 did not directly induce LTB(4) release, nor was lypoxigenase expression augmented. Preincubation of RAGMs with NDGA (nordihydroguiaretic acid) (10(-5)M) completely abolished the production of LTB4 on RAGMSs challenged with A23187 in combination with RANTES or A23187 alone in the supernatants. Similar effects were obtained when the cells were pretreated with dexamethasone. These data suggest, for the first time, that RANTES may stimulate the release of LTB(4), only when it is associated to other stimuli and for this reason we conclude that RANTES modulates inflammatory diseases, and may require other stimuli to be effective in amplifying its spectrum of action(s).
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Activation of cytokine receptors and alterations in cytokines are thought to play important roles in neuronal dysfunction and in the pathogenesis of the nervous system diseases. CXCL8 (IL-8) is a CXC chemokine with chemotactic and... more
Activation of cytokine receptors and alterations in cytokines are thought to play important roles in neuronal dysfunction and in the pathogenesis of the nervous system diseases. CXCL8 (IL-8) is a CXC chemokine with chemotactic and inflammatory properties. Chemokines control mast cell infiltration in several inflammatory diseases, including stress and neurological dysfunctions. Using isolated human umbilical cord blood-derived cultured mast cells (HUCMC) from hematopoietic stem cells CD34+, mast cells were immunologically activated with anti-IgE at concentrations of 1, 5, 10 and 20 microg/ml leading to the dose-dependent production of IL-8 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The increase in IL-8 mRNA expression was also noted when the cells were treated with anti-IgE at 10 microg/ml for 6 h. Immunologically activated HUCMC provoked the generation of tryptase in a dose- and time-dependent manner. We also found increased histidine decarboxylase (HDC) expression in activated HUCMC after 6 h of incubation, a rate-limiting enzyme responsible for the generation of histamine from histidine. Taken together, these results confirm that anti-IgE-activated mast cells release inflammatory mediators including CXCL8, a CXC chemokine which regulates several biological effects of mast cells, e.g. chemoattraction, and possibly causes cell arrest.
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Research Interests: Electron Microscopy, Microcirculation, Mitochondria, Microvascular Physiology, Capillaries, and 10 moreAnimals, Male, Heart, Perfusion, Clinical Sciences, Rats, Myocardium, Wistar Rats, Reperfusion injury, and Simvastatin(Animals, Male, Heart, Perfusion, Clinical Sciences, Rats, Myocardium, Wistar Rats, Reperfusion injury, and Simvastatin)
(Animals, Male, Heart, Perfusion, Clinical Sciences, Rats, Myocardium, Wistar Rats, Reperfusion injury, and Simvastatin)
This study evaluates the immune response to ingestion of 10 mg of nickel (Ni) (as Ni sulphate) in 19 young non-atopic Ni-sensitised or 9 non-allergic women (group A). After Ni ingestion at 8 a.m, non-allergic and 12 Ni-sensitised women... more
This study evaluates the immune response to ingestion of 10 mg of nickel (Ni) (as Ni sulphate) in 19 young non-atopic Ni-sensitised or 9 non-allergic women (group A). After Ni ingestion at 8 a.m, non-allergic and 12 Ni-sensitised women (group B) were non-symptomatic, while 7 Ni-sensitised women (group C) showed a flare up of urticaria and/or eczema. Serum and urine Ni were greatly lower before Ni administration than after 4 and 24 hours, without difference among the 3 groups. Before treatment, group B and C showed higher values of blood CD19+ and CD5--CD19+ cells than group A, while group C showed higher serum interleukin (IL) 2 and lower serum IL-5. Four hours after Ni ingestion, group C showed significant increase in serum IL-5. Twenty-four hours after treatment, group A showed a significant reduction in blood CD4+-CD45RO- &quot;virgin&quot; cells and an increase of CD8+ lymphocytes, while group C showed a marked decrease in total blood lymphocytes and CD3+, CD4+-CD45RO-, CD4+-CD45RO+, CD8+, CD19+ and CD5--CD19+ cell subsets. These data may be explained with migration of lymphocytes in tissues with a Th0-like immune response, as shown by the elevated serum IL-2 and the increase of serum IL-5 during the test.