Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analysed the cytokine profile of a T cell subset (CD4+ CD45 RC-) that confers protection against Trichinella spiralis infection in rats. These CD4+ cells are generated in the gut and appear in the thoracic duct lymph within 72 h after infection. Cytokine mRNA levels for IL-2, IL-3, IL-4, IL-5, IL-10 and IFN-gamma and functional cytokine secretion for IL-4, IL-5, IFN-gamma, TNF-alpha and mast cell differentiation activity were tested in vitro following stimulation with T. spiralis antigens. Compared to a non-protective T cell population (CD4+ CD45 RC+ or CD8+), also isolated from the same thoracic lymph, no significant differences were observed in the levels of mRNA for IL-2, IL-3, IL-4, IL-5, IL-10 or IFN-gamma in the protective CD4+ CD45 RC- cells. However, analysis of the cytokine activities in culture supernatant of these T cell subsets following 24 h stimulation in vitro with T. spiralis antigens showed that significant IL-4 and IL-5 activity but little IFN-gamma or TNF-alpha was secreted by the protective CD4+ CD45- RC- cells. Whereas the non-protective CD4+ CD45 RC+ cells secreted significant levels of IL-4, IFN-gamma, mast cell differentiating activity and TNF-alpha but little IL-5 activity. Non-protective CD8+ cells were found to secrete IL-4 but not IL-5. Production of IL-4 was essentially equal for both protective and non-protective T cell subsets. These findings suggest that the presence or absence of IFN-gamma secretion, rather than IL-4 alone, determines whether a T cell subset has protective activity against T. spiralis infection in rats.
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PMID:Cytokine profile of protective anti-Trichinella spiralis CD4+ OX22- and non-protective CD4+ OX22+ thoracic duct cells in rats: secretion of IL-4 alone does not determine protective capacity. 780 64

In allergic diseases, exposure of sensitized subjects to allergen induces the activation of tissue mast cells that results in an immediate-type hypersensitivity response and, in some individuals, a a late phase response. We previously have reported that the neutrophil infiltration associated with IgE-dependent cutaneous inflammation in mice is mast cell-dependent and that TNF-alpha contributes significantly to this response. We report here that either dexamethasone or cyclosporin A can inhibit mouse mast cell TNF-alpha production in vitro, and that these agents also can significantly suppress the tissue swelling and leukocyte infiltration associated with two forms of TNF-alpha-associated inflammation in vivo: the entirely IgE- and mast cell-dependent inflammation at sites of passive cutaneous anaphylaxis reactions and the entirely TNF-alpha-dependent inflammation that is elicited by the direct intradermal injection of recombinant mouse TNF-alpha. Taken together, our in vitro and in vivo findings in mice indicate that dexamethasone or cyclosporin A can have at least three actions that interfere with the pathogenesis of IgE, mast cell, and cytokine-dependent inflammatory reactions:suppression of the IgE-dependent increase in TNF-alpha mRNA by mast cells, inhibition of the IgE-dependent production of TNF-alpha protein by mast cells, and diminution of the responsiveness of target cells to TNF-alpha. Our findings in mice raise the possibility that similar actions of these agents in humans may account for some of the clinical efficacy of corticosteroids and cyclosporin A in allergic diseases.
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PMID:Dexamethasone or cyclosporin A suppress mast cell-leukocyte cytokine cascades. Multiple mechanisms of inhibition of IgE- and mast cell-dependent cutaneous inflammation in the mouse. 782 5

The skin is a major target organ for graft-versus-host disease (GVHD), the principal complication of allogeneic bone marrow transplantation. The purpose of the present study was to test whether mast cell degranulation might be related to early target cell injury in the development of acute GVHD. We employed two irradiated murine strain combinations, one in which disease was mediated by CD4+ effector T cells (B10.D2-->DBA/2), and the other by CD8+ effector T cells (B10.BR-->CBA). As compared to controls, both models exhibited mast cell degranulation of differing extents and patterns, as well as dyskeratosis in the epidermis before the influx of effector lymphocytes. These results suggested that factors produced and released by degranulated dermal mast cells might contribute to early target cell injury. Accordingly, the possible role of tumor necrosis factor (TNF)-alpha, a cytokine recently discovered in mast cell granules, was investigated by the injection of anti-TNF-alpha antibody during the course of disease mediated by either CD4+ or CD8+ T cells. Although overall survival of recipients undergoing CD4+ T-cell-mediated GVHD was only slightly improved and the extent of mast cell degranulation was not affected by anti-TNF-alpha antibody treatment, the skin exhibited a significant diminution in the number of dyskeratotic cells/linear mm at 3-4 weeks post-transplantation. In contrast, anti-TNF-alpha antibody failed to enhance survival or reduce the number of dyskeratotic cells in the skin during CD8+ T-cell-mediated disease. Finally, to determine whether CD8+ T-cell-mediated GVHD was at all dependent upon mast cell involvement, the C3H.SW-->B6WWv strain combination was utilized, in which recipients were genetically deficient in mast cells. Onset of GVHD was significantly delayed in B6WWv mice and was clearly correlated to the appearance and increase of de novo mast cells at later time points.
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PMID:Role of mast cells in early epithelial target cell injury in experimental acute graft-versus-host disease. 790 82

Changes in blood-nerve barrier (BNB) integrity and nerve conduction were assessed in rat tibial nerves in which mast cell degranulation was induced by intraneural injection of Compound 48/80 (C48/80). BNB permeability changes were quantitated by the endoneurial accumulation of Evan's blue-labelled albumin (EBA). Over 24 h following intraneural injections, nerves receiving saline showed a 6-fold increase in endoneurial extravasated EBA compared to non-injected nerves. Injection of 250 ng C48/80 produced a similar level of EBA accumulation as saline injections. Increasing the C48/80 dose to 1 microgram produced twice the EBA accumulation as control saline injections and a 12-fold increase over non-injected nerves. Tibial nerves injected with these C48/80 doses showed completely normal nerve conduction. In contrast, increasing the dose to 5 micrograms C48/80 induced, again, increased EBA accumulation over lower doses, but also significant axonal degeneration indicated by profound decreases in compound muscle action potential amplitudes measured with nerve stimulation distal to the injection site. Co-injection of Leupeptin and neutralizing anti-TNF-alpha antibodies with C48/80 failed to mitigate conduction abnormalities suggesting a direct toxic effect of C48/80 on nerve fibres. Time-kinetic studies showed rapid restoration of BNB integrity 24-48 h after injections in all nerves, but at these timepoints C48/80 injected nerves still showed significantly increased BNB permeability compared to nerves injected with saline. Neural mast cell stimulation in the absence of a primed immune response can produce profound temporary changes in blood-nerve barrier permeability and endoneurial fluid composition without affecting nerve conduction.
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PMID:Effects of mast cell degranulation on blood-nerve barrier permeability and nerve conduction in vivo. 796 79

The human basophilic cell line KU 812, that also has some mast cell characteristics, was found to express the PDGF-A gene and secrete PDGF-A like activity. After treatment with IL-6+ TNF-alpha, the PDGF-A mRNA expression increased as did cytoplasmic immunostaining with anti-PDGF antibodies. Secretion of PDGF-A was visualized by immunoprecipitation. An augmentation of non-secreted PDGF-like activity after IL-6+ TNF-alpha treatment was not accompanied by induction of the long splice variant of the PDGF-A-chain mRNA. Treatment with TPA caused an increase in PDGF-A expression and in addition, an induction of PDGF-B transcripts were seen. Staining of cytospin preparations with anti-PDGF antibodies visualized a substantial increase in immunostaining of the TPA treated cells and both intracellular and secreted PDGF-AA-like activity was substantially increased as compared to untreated control cultures. There was a concomitant induction of exon 6 specific mRNA, corresponding to a cellular retention signal after TPA treatment. Our results show that PDGF can be produced by a cell line of the basophilic/mast cell lineage, i.e. cells involved in allergic disorders and inflammation.
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PMID:Constitutive and inducible expression of PDGF in the human basophilic cell line, KU 812. 827

Recent findings indicate that mast cells can influence biological responses through the production of cytokines and suggest that many allergic reactions and other biological processes may be regulated by a "mast cell-leukocyte cytokine cascade". This hypothesis proposes that certain biological responses are initiated by mast cell activation, resulting in the mast cell-dependent release of TNF-alpha and other cytokines which can promote the recruitment of eosinophils, neutrophils, and other effector cells. The recruited effectors then influence the progression of the response by providing additional sources of some cytokines which also can be elaborated by mast cells, as well as by producing other cytokines not known to be of mast cell origin.
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PMID:Mast cell cytokines in allergy and inflammation. 836 64

Allergic mucosal inflammation is characterized by the presence of cell infiltration, predominantly with IgE-sensitized mast cells and activated eosinophils, and appears to be regulated by the local production and release of several cytokines, particularly IL-4 and IL-5. Although attention has focused on the Th2 subpopulation of CD4+ T lymphocytes as an important source of these cytokines, human mast cells have been shown to both store and secrete IL-4 and TNF-alpha. To investigate the expression of cytokines relevant to allergic inflammation and to identify their cellular localization within the nasal mucosa, we have undertaken specific immunohistochemical staining of thin sections of inferior turbinate biopsies from patients with perennial allergic rhinitis and, for comparison, from nonatopic healthy volunteers. The cytokines investigated were IL-4, IL-5, IL-6, and IL-8. In both the normal and rhinitic biopsies numerous cells immunoreactive for IL-4, IL-5, and IL-6 were seen. Staining of adjacent 2-microns sections for CD3, mast cell tryptase, and eosinophil cationic protein revealed that 90% of the IL-4 immunoreactive cells were mast cells, with biopsies from rhinitic subjects containing significantly more IL-4+ cells than biopsies from normal controls (p = 0.02), especially when assessed with the anti-IL-4 mAb 3H4. Mast cells also accounted for > 90% of IL-6 and > 50% of IL-5 immunoreactive cells. IL-5 immunoreactivity was also localized to eosinophils, whereas IL-8 localized predominantly to the nasal epithelium in both groups. No cytokines were found in association with T lymphocytes. These findings indicate that the mast cell is an important source of preformed cytokines and as such may contribute to the chronicity of the mucosal inflammation that characterizes allergic rhinitis.
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PMID:Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation. 837 6

We have examined the effects of mercuric chloride (HgCl2) on growth and IL-4, IL-8, TNF-alpha and MHC class II gene expression in the HMC-1 human leukemic mast cell line. Proliferation, measured by [3H]thymidine incorporation or production of a formazan product (MTT assay), was substantially inhibited by HgCl2 at concentrations of 10(-6) M and above. Inspection of the DNA by agarose gel electrophoresis from HgCl2-treated cells revealed that it was intact, indicating inhibition of DNA synthesis, but not denaturation. HgCl2 inhibited expression of mRNA for IL-8, TNF-alpha and MHC class II at 4 x 10(-6) M and inhibited expression of IL-4 mRNA at 8 x 10(-6) M and above. At a concentration of 10(-5)M, HgCl2 almost completely blocked mRNA expression for IL-4, IL-8, TNF-alpha and MHC class II, but produced negligible inhibition of expression of mRNA encoding the housekeeping gene beta-actin, thus demonstrating selective toxicity for the cytokine and MHC class II genes studied. Pre-exposure of the cells to human recombinant IL-4 prior to treatment with HgCl2 had no effect on expression levels of any of the genes examined. The effects seen in this study are consistent with previous reports showing immunotoxic effects of HgCl2 on other cell types, therefore, the HMC-1 mast cell line may prove useful in further studies of mast cell cytokine gene expression and the mechanisms involved in cytokine gene toxicity.
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PMID:The effects of mercuric chloride on growth, cytokine and MHC class II gene expression in a human leukemic mast cell line. 856 Apr 97

Sulfasalazine is an effective treatment in some inflammatory diseases that exhibit mast cell (MC) hyperplasia. However, its effect on MC has been incompletely studied. We have established that sulfasalazine inhibits the release of histamine and TNF-alpha from MC. Sulfasalazine and its metabolites, 5-aminosalicylic acid (5-ASA) and to a lesser extent sulfapyridine, inhibited Ag-stimulated histamine release from rat peritoneal MC in a concentration-dependent manner with a 50% inhibitory concentration of 6 x 10(6)M, 8 x 10(-6)M, and 3 x 10(-4)M, respectively. Similar results were observed with sulfapyridine and 5-ASA on Ag-stimulated histamine release of another population of MC, namely rat intestinal mucosal MC, but sulfasalazine was markedly less potent than its metabolites. Interestingly, sulfasalazine and sulfapyridine, but not 5-ASA, inhibited Ag-stimulated TNF-alpha released by MC. Similar results were observed with MC-mediated cytotoxic activity in which sulfasalazine and sulfapyridine, but nor 5-ASA, inhibited MC TNF-alpha-dependent cytotoxicity in a concentration-dependent manner. The addition of sulfasalazine to MC, up to 12 h after the cytotoxic assay (16 h) had started, significantly inhibited cytotoxic activity, suggesting that sulfasalazine inhibited the cytotoxic mediator, TNF-alpha. Indeed, affinity studies demonstrated that sulfasalazine binds TNF-alpha. Furthermore, the inhibition of MC cytotoxicity by sulfasalazine appeared to require new protein synthesis. Pretreatment of MC with sulfasalazine also inhibited the release of TNF-alpha and reduced the levels of TNF-alpha mRNA. Thus, sulfasalazine inhibits MC-mediated, TNF-alpha-dependent cytotoxicity by multiple mechanisms: competitive inhibition of soluble TNF-alpha, reduction of levels of TNF-alpha mRNA, and inhibition of TNF-alpha release.
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PMID:Inhibitory effects of sulfasalazine and its metabolites on histamine release and TNF-alpha production by mast cells. 859 65

Mast cells have been traditionally associated with an acute allergic response. However, their role in regulating chronic inflammatory processes must also be considered in view of evidence that mast cells synthesize and release a number of cytokines. In this study, we have examined the effect of cholera toxin (CT) on peritoneal mast cell IL-6 and TNF-alpha production. Highly purified, freshly isolated, rat peritoneal mast cells from Brown Norway rats were cultured in the presence of CT or its B subunit (CTB) alone or in combination with anti-IgE or bacterial LPS. Histamine release was measured after 10 min; IL-16 and TNF-alpha production was assessed in supernatants after 18 h. We found that CT or CTB alone did not affect histamine release; however, mast cell IL-6 production was significantly enhanced by CT but not by CTB. In contrast, constitutive production of TNF-alpha was inhibited by CT. The effects of CT were similar to our previous observations of the actions of prostaglandin E2 on mast cells. We also examined the effects of CT in combination with other mast cell activating agents. CT had no significant effect on anti-IgE-induced histamine release. An additive effect on IL-6 production was observed in the context of LPS. Forskolin, an agent known to increase intracellular cAMP levels, also induced a significant increase in IL-6 production, whereas TNF-alpha production was decreased. These data have important implications for our understanding of the regulation of mast cell cytokine production and the effects of CT on local cytokine production.
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PMID:Cholera toxin increases IL-6 synthesis and decreases TNF-alpha production by rat peritoneal mast cells. 859 79


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