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)

The ability of subcutaneously (s.c.) injected cytokines (IL-4, IL-5, IL-6, IFN alpha, IFN gamma, GMCSF) to regulate the induction of hapten-specific immediate hypersensitivity (IH) responses was studied in BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) sensitized BALB/c mice at the peak of a hapten-specific IgE antibody forming cell (AFC) response. To induce IH responses, mice were injected in the right pinna with either BPO-BSA (benzylpenicilloyl-bovine serum albumin), BPO-KLH (0.01-1.0 micrograms/ml) or mcAb anti-IgE (0.001 - 1.0 micrograms/ml); and in the left pinna with an equal volume of saline (0.05 ml). Pinnae were measured 5 min to 4 hr later using a micrometer caliper. Treatment of mice with IL-4 or IFN gamma dramatically suppressed the induction of IH responses in dose dependent fashion. In contrast, treatment of mice with IL-6 and IFN alpha increased these responses in dose dependent fashion, while GMCSF and IL-5 had no effect. The suppression obtained with IL-4 and IFN gamma, and the increases seen with IL-6 and IFN alpha, were transient since these cytokines, as well as GMCSF and IL-5, had no effect on IH responses elicited 21 days after the peak of BPO-specific IgE AFC responses. The data suggest that cytokine mediated effects on IH responses occur via changes in serum levels of BPO-specific IgG1 or IgE, through direct or indirect effects of cytokines on mast cells or other cell types, or by affecting the ability of BPO-specific homocytotropic antibodies to bind to mast cell surfaces.
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PMID:Cytokine-induced suppression and potentiation of hapten-specific immediate hypersensitivity responses. 768 21

Interleukin 9 (IL-9) is a TH2 cytokine that has been shown to promote the antigen-independent growth of some mouse T helper clones. To characterize the specificity of IL-9-mediated T cell activation, we used a murine T cell clone that could grow with either IL-9 or IL-2. After differential hybridization of a cDNA library, we isolated three genes that were expressed preferentially in the presence of IL-9. Two of them correspond respectively to granzyme A and granzyme B, two proteases expressed by activated T cells. By Northern blot hybridization and functional assays, we found that IL-9 induced the expression of granzyme B in several T cell clones as well as in mast cell lines. In addition, other proteases such as the mouse mast cell proteases were also found to be expressed by IL-9-activated T cell clones. The third IL-9-induced cDNA corresponds to the alpha-chain of the high-affinity receptor for IgE. Several T cell clones expressed this IgE receptor mRNA and were able to bind IgE with high affinity. Taken together, our results indicate that IL-9 induces a mast cell-like phenotype in T cell clones.
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PMID:IL-9 induces expression of granzymes and high-affinity IgE receptor in murine T helper clones. 773 Jun 12

Endobronchial biopsy and lavage studies have revealed the presence of mast cell, eosinophil, T-lymphocyte and epithelial cell activation in asthma, along with the structural changes of tissue eosinophil infiltration, loss of superficial columnar ciliated epithelial cells and enhanced collagen deposition in the laminar reticularis. As these cellular and structural changes underlie the clinical features of asthma, i.e., symptom expression, variable airflow obstruction and bronchial hyperresponsiveness, and understanding of their induction and regulation is essential to the understanding of the asthmatic process. The acute airway response to allergen has been studied by the technique of local endobronchial allergen challenge with direct airway sampling in asthma. These studies identify allergen-mast cell interaction as the initial airway event, with mediator release inducing bronchoconstriction and enhancing vascular permeability. As preformed cytokines are present in mast cells, cytokine release from this cell population is likely to initiate the process of endothelial cell activation, with upregulation of cell adhesion molecules, and tissue cell recruitment. Subsequent cytokine elaboration from airway macrophages and T-lymphocytes will perpetuate this response while in chronic clinical disease T-lymphocytes, mast cells, matrix tissue, epithelial cells and eosinophils themselves are all likely to contribute to the cytokine pool within the airways and thus to the regulation of inflammatory cell migration and activation.
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PMID:The airway inflammatory response in allergic asthma and its relationship to clinical disease. 779 34

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 molecular basis for the commitment of multipotential myeloid progenitors to the eosinophil lineage, and the transcriptional mechanisms by which eosinophil-specific genes are subsequently expressed and regulated during eosinophil development are currently unknown. Interleukin-5 (IL-5) is a T cell and mast cell-derived cytokine with actions restricted to the eosinophil and closely related basophil lineages in humans. The high affinity receptor for IL-5 (IL-5R) is composed of an alpha subunit (IL-5R alpha) expressed by the eosinophil lineage, that associates with a beta c subunit shared with the receptors for IL-3 and granulocyte-macrophage colony stimulating factor (GM-CSF). As a prerequisite to studies of the transcriptional regulation of the IL-5R alpha subunit gene, we used three different methods, including primer extension, RNase protection, and 5'-RACE to precisely map the transcriptional start site to a position 15 base pairs (bp) upstream of the 5' end of the published sequence of IL-5R alpha exon 1. To initially identify the IL-5R alpha promoter, 3.5 kilobases (kb) and 561 bp of the 5' sequence flanking the transcriptional start site were subcloned into the promoterless pXP2-luciferase vector. Transient transfection of these constructs into an eosinophil-committed HL-60 subline, clone HL-60-C15, induced the expression of approximately 240-fold greater luciferase activity than the promoterless vector, identifying a strong functionally active promoter region within the 561 bp of sequence proximal to the transcriptional start site and with activity equivalent to pXP2 constructs containing the entire 3.5 kb of upstream sequence. To more precisely localize the cis-acting regulatory elements in this region important for promoter activity, a series of 5' deletion mutants of the 561-bp region were generated in the pXP2-luciferase vector. Deletion of the region between bp -432 and -398 reduced promoter activity by more than 80% in the HL-60-C15 cell line. Further analyses of the activity of the IL-5R alpha promoter constructs in various other eosinophil, myeloid, and non-myeloid cell lines indicated that the promoter was relatively myeloid and eosinophil lineage-specific in its expression. Consensus sequences for known transcription factor binding sites were not present in the 34-bp region of the promoter required for maximal activity, suggesting unique myeloid- and possibly eosinophil-specific regulatory elements.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Identification and characterization of a functional promoter region in the human eosinophil IL-5 receptor alpha subunit gene. 783 16

Allergic symptoms result from the release of granular and lipidic mediators and of cytokines by inflammatory cells. The whole process is initiated by the aggregation of mast cell and basophil high-affinity IgE receptors (Fc epsilon RI) by IgE and antigen. We report here that IgE-induced release of mediator and cytokine can be inhibited by cross-linking Fc epsilon RI to low-affinity IgG receptors (Fc gamma RII) which are constitutively expressed on mast cells and basophils. Using a model of stable transfectants in RBL-2H3 cells expressing endogeneous rat Fc epsilon RI and recombinant murine Fc gamma RII, we showed that inhibition requires that Fc epsilon RI be crosslinked to Fc gamma RII by the same multivalent ligand. Inhibition of cross-linked receptors left non-cross-linked Fc epsilon RI capable of triggering mediator release and was reversible upon disengagement. Both isoforms of wild-type Fc gamma RII were equally capable of inhibiting Fc epsilon RI-mediated mast cell activation provided they had an intact intracytoplasmic domain. Our results demonstrate that mast cell secretory responses triggered by high-affinity receptors for IgE may be controlled by low-affinity receptors for IgG. This regulation of Fc epsilon RI-mediated mast cell activation is of potential interest in mast cell physiology and in allergic pathology.
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PMID:Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors. 786 Jul 41

Interleukin-9 (IL-9) is a multifunctional cytokine produced by activated TH2 clones in vitro and during TH2-like T cell responses in vivo. The IL-9 receptor is a member of the hemopoietin receptor superfamily and interacts with the gamma chain of the IL-2 receptor for signal transduction. Various observations indicate that IL-9 is actively involved in mast cell responses by inducing the proliferation and differentiation of these cells. The role of IL-9 in T cell responses is less clear. Although freshly isolated normal T cells do not respond to IL-9, this cytokine induces the proliferation of murine T cell lymphomas in vitro and in vivo overexpression of IL-9 results in the development of thymic lymphomas. In the human, the existence of an IL-9-mediated autocrine loop has been suggested for some malignancies such as Hodgkin's disease. Other potential biological targets for IL-9 include B lymphocytes, hematopoietic progenitors, and immature neuronal cell lines.
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PMID:Interleukin-9 and its receptor: involvement in mast cell differentiation and T cell oncogenesis. 788 4

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

The cytokine interleukin (IL) 12 stimulates T cell and natural killer cell production of interferon (IFN) gamma and inhibits T cell production of IL-4. We investigated the effects of IL-12 on cytokine gene expression, immunoglobulin (Ig)E, mucosal mast cell, and eosinophil responses, and the course of infection in mice inoculated with the nematode parasite Nippostrongylus brasiliensis, as well as the IFN-gamma dependence of these effects. IL-12 stimulated IFN-gamma and IL-10 gene expression during primary and secondary N. brasiliensis infections and inhibited IL-3, IL-4, IL-5, and IL-9 gene expression during primary infections but had little inhibitory effect during secondary infections. IL-12 inhibited IgE, mucosal mast cell, and blood and tissue eosinophil responses during primary infections, but only eosinophil responses during secondary infections. IL-12 enhanced adult worm survival and egg production during primary, but not secondary infections. IL-12 needed to be administered by day 4 of a primary infection to inhibit IgE and mucosal mast cell responses, and by day 6 to strongly inhibit eosinophil responses and to enhance worm survival and fecundity. Anti-IFN-gamma mAb inhibited the effects of IL-12 on IgE secretion, intestinal mucosal mastocytosis, and parasite survival and fecundity, but did not affect IL-12 inhibition of eosinophilia. These observations indicate that IL-12, if administered during the initiation of eosinophilia. These observations indicate that IL-12, if administered during the initiation of an immune response, can change the response from one that is characterized by the production of T helper (Th)2-associated cytokines to one characterized by the production of Th-1 associated cytokines. However, IL-12 treatment has less of an effect once the production of Th2-associated cytokines has become established. In addition, our results provide evidence that Th2-associated responses protect against, and/or Th1-associated responses exacerbate, nematode infections.
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PMID:Effects of interleukin 12 on immune responses and host protection in mice infected with intestinal nematode parasites. 816 28


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