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)

Although transcription of mast cell (MC) secretory granule neutral protease genes has been shown to distinguish MC subclasses in mucosal and serosal environments, the specific cytokines that regulate the expression of these genes have not been determined. To examine cytokine-mediated gene regulation, bone marrow-derived MC (BMMC) differentiated in vitro were obtained by culturing mouse bone marrow progenitor cells in the presence of WEHI-3 cell-conditioned medium, concanavalin A-stimulated splenocyte-conditioned medium (BMMCC), or recombinant (r) interleukin (IL)-3 (BMMCIL-3). All three populations of BMMC expressed the serosal MC-specific transcripts that encode mouse MC serine protease (MMCP)-5, MMCP-6, and MC carboxypeptidase A. However, only BMMCC contained MMCP-2 mRNA, a late expressed gene selectively transcribed by intestinal mucosal MC that proliferate during helminthic infestation in response to the T cell-derived cytokines IL-3, IL-4, and IL-10. When BMMCIL-3 were exposed to rIL-10 in the presence of either rIL-3 or rIL-4, they expressed MMCP-2 mRNA. Not only was the transcription of the MMCP-2 gene in BMMC dependent on continuous exposure of the cells to rIL-10, but the level of MMCP-2 mRNA in these cells could be down-regulated by rIL-3. These studies comparing the effects of two cytokines on the transcriptional regulation of secretory granule protease genes in MC demonstrate that rIL-10 induces BMMCIL-3 to express the mucosal MC protease MMCP-2, that rIL-3 attenuates the rIL-10-induced expression of this gene, and that transcription of the MMCP-2 gene is reversed in the absence of rIL-10.
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PMID:Transcriptional regulation of the mucosal mast cell-specific protease gene, MMCP-2, by interleukin 10 and interleukin 3. 156 97

The relationship between production of IgE and collagen-induced arthritis in mice was examined. Collagen-specific IgE was produced as a consequence of immunization of DBA/1 mice with chicken type II collagen emulsified in CFA. We observed a rise in collagen-specific IgE antibody levels at the onset of CIA clinical and histologic signs in DBA/1 mice. This rise in IgE paralleled that of IgG2a anticollagen antibodies, an isotype implicated in the pathogenesis of CIA by other laboratories. The collagen-specific IgE contained in the plasma of mice with CIA could arm basophils for Ag- (collagen) dependent degranulation. Collagen-specific IgE may thus contribute to CIA by promoting mast cell degranulation in the synovia of susceptible mice immunized with chick type II collagen; but, further work is required to establish such a role for IgE in CIA. However, genetic differences in disease susceptibility could not be accounted for by quantitative differences in collagen-specific IgE production. Further, comparable levels of IgE anticollagen antibodies were observed in animals with active CIA and after spontaneous remission, thereby confirming that the presence of such antibodies is insufficient for disease. Total IgE levels peaked just before spontaneous remission indicating active production of IL-4. IL-4 was administered to animals with CIA to determine if this lymphokine could be involved in the remission process. IL-4 facilitated remission of CIA. Enhanced total IgE production may thus be a marker for activation of Th2 cells that produce lymphokines such as IL-4 and IL-10, factors that may be involved in the spontaneous remission process.
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PMID:Collagen-induced arthritis in mice. Relationship of collagen-specific and total IgE synthesis to disease. 175 95

We investigated the increase in mast cell numbers at the sites of inoculation of keratinocyte-derived squamous cell carcinoma cell line (KCMH-1) cells in mice. A significant increase in the number of mast cells was observed at the sites of tumours developed at the sites of inoculation of the KCMH-1 cells. Enhancement of mast cell growth was observed by culturing bone marrow-derived mast cells (BMMC) on NIH/3T3 fibroblast monolayers in the presence of conditioned medium (TCM) obtained from KCMH-1. Activities of known factors for mast cell growth, such as interleukin-3 (IL-3), IL-4, IL-9, IL-10 and stem cell factor (SCF), were not detected in the TCM. Nerve growth factor (NGF) did not induce mast cell growth. Mast cell growth induced by the TCM needed 3T3 fibroblasts. These results suggest that KCMH-1 cells may produce a factor which induces mast cell growth with 3T3 fibroblasts, other than the already known mast cell growth factors. This may be the mechanism of mast cell accumulation at sites of tumours.
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PMID:Enhancement of fibroblast-dependent mast cell growth in mice by a conditioned medium of keratinocyte-derived squamous cell carcinoma cells. 753 34

Cytokines represent the major factors involved in the communication between T cells, macrophages and other immune cells in the course of an immune response to antigens and infectious agents. A number of studies on mouse and human T helper (Th) clones have recently provided extensive evidence for the existence of different activities exhibited by Th cells (called Th1 and Th2), which was apparently inferred from the profile of cytokine secretion. The Th1-type immune response is generally associated with IgG2a production and the development of cellular immunity, the Th2-type response with IgE production, eosinophils and mast cell production. This review focuses on the role of different cytokines produced by macrophages (especially interferons (IFNs), TNF-alpha, IL-10 and IL-12) or T cells (IFNs, IL-2, IL-4, IL-10, IL-13 and TGF-beta) in macrophage-T cell interactions and the cytokine relevance in the differentiation of Th cells towards the Th1 or Th2 type of immune response. Th1-derived cytokines (IFN-gamma, IL-2, TNF-alpha) favor macrophage activation, whereas the Th2 cytokines (IL-4, IL-10, IL-13) exhibit suppressive activities on macrophage functions. A key role in the differentiation towards the Th1-type response is now attributed to IL-12, a recently described cytokine produced mainly by macrophages. Its production can be upregulated by IFN-gamma and is inhibited by IL-10 and IL-4. All this emphasizes the importance of macrophage-cytokine interactions in determining the type of immune response. This article also aims to review recent data concerning the roles of IFNs alpha/beta (type I) and IFN-gamma (type II) in the regulation of the immune response. While there is much information on the regulatory effects of IFN-gamma (also called "immune IFN") on the immune response, little is so far known of the role of type I IFNs. These cytokines, originally described as simple antiviral substances, are now taken to be important regulators of the immune response. Recent data indicate that these molecules (especially IFNs-alpha) specifically promote the differentiation towards the Th1-type response. The stimulatory effects of IFN-alpha on the generation of the Th1-type response may be involved in its therapeutic effects in some human diseases, including early AIDS, hypereosinophilia and certain tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of interferons and other cytokines in the regulation of the immune response. 753 71

To study cytokine regulation of the 5-lipoxygenase (5-LO)/leukotriene (LT) synthase pathway we have developed mouse bone marrow-derived mast cells (BMMC) that minimally express each protein of the pathway by using a novel culture system, lacking interleukin (IL)-3. When mouse bone marrow cells were cultured for 5 weeks with 100 ng/ml c-kit ligand (KL) and 10 units/ml IL-10, a population of > 95% mast cells was obtained. These cells generated 8.3 +/- 4.5 ng of LTC4/10(6) cells and 8.1 +/- 2.4 ng of prostaglandin (PG) D2/10(6) cells after IgE-dependent activation. When these BMMC were cultured for 2-5 weeks more with 100 units/ml IL-3 in the continued presence of KL and IL-10, the IgE-dependent generation of LTC4 and PGD2 increased to 212 +/- 36 and 25.5 +/- 8.6 ng/10(6) cells, respectively. The dramatic increase in the IgE-dependent generation of LTC4 in response to IL-3 was accompanied by a concomitant increase in expression of 5-LO and 5-LO-activating protein and preceded the increased expression of cytosolic phospholipase A2 and LTC4 synthase. The recognition that IL-3 up-regulates the expression of each protein of the 5-LO pathway for the generation of LTC4 contrasts with our recent finding that KL up-regulates the expression of cytosolic phospholipase A2, prostaglandin endoperoxide synthase-1, and hematopoietic PGD2 synthase and increases the IgE-dependent generation of PGD2 in BMMC developed from bone marrow with IL-3. Thus, developmentally segregated regulation of the prostanoid and cysteinyl leukotriene pathways in lineage-related committed mast cell progenitors reveals the pleiotropism of this effector cell of allergic inflammation, a cytokine/growth factor basis for preferential expression of pathways of eicosanoid biosynthesis, and the particular role of IL-3 in regulating the expression of the proteins of the 5-LO/LTC4 synthase pathway.
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PMID:Interleukin-3 regulates development of the 5-lipoxygenase/leukotriene C4 synthase pathway in mouse mast cells. 755 81

Although the immune responses to intestinal nematode infection have been well studied and have been shown to be strongly driven by Th2-associated cytokines in mice, such information has been limited with respect to rats. We investigated changes in levels of the mRNAs encoding interleukin-2 (IL-2), IL-3, IL-4, IL-5, IL-10, and gamma interferon in the mesenteric lymph nodes of rats infected with Nippostrongylus brasiliensis by reverse transcription-PCR in comparison with immunoglobulin E (IgE)/IgG2a antibody, eosinophil, basophil, and mucosal mast cell responses. In the two rat strains used, Brown Norway and Fischer-344, which show different responses to allergens, serum IgE increased to much higher levels in the former than in the latter 2 weeks after infection. Intestinal mastocytosis was observed much earlier and more intensely in Brown Norway rats than in Fischer-344 rats, but the degrees of peripheral eosinophilia and basophilia did not differ between the two strains. In both strains, IL-3, IL-4, and IL-5 mRNA expression increased and peaked around 7 to 14 days after infection, while expression of IL-2, IL-10, and gamma interferon mRNAs did not change notably throughout the experimental period. The highest IL-4 mRNA expression was observed slightly earlier in Brown Norway than in Fischer-344 rats, but levels of IL-3 and IL-5 mRNAs peaked synchronously in both strains. The amounts of mRNAs encoding these three cytokines were always higher in Brown Norway than in Fischer-344 rats. It is suggested that in rats, Th2 or Th2-like cells are also induced after nematode infection, and IgE elevation is mainly related to increased IL-4 gene expression.
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PMID:Cytokine mRNA expression profiles in rats infected with the intestinal nematode Nippostrongylus brasiliensis. 759 Nov 19

In the last few years evidence has been accumulated to suggest that allergen-reactive type 2 T helper (Th2) cells play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells and eosinophils, the cellular triad involved in the allergic inflammation. Interleukin (IL)-4 production by a still unknown cell type (T-cell subset, mast cell/basophil?) at the time of antigen presentation to the Th cell is critical for the development of Th2 cells. Other cytokines, such as IL-1 and IL-10, and hormones, such as calcitriol and progesterone, also play a favoring role. In contrast, cytokines such as interferon-alpha, interferon-gamma, IL-12 and transforming growth factor-beta, and hormones, such as dehydroepiandrostenone, play a negative regulatory role in the development of Th2 cells. However, the mechanisms underlying the preferential activation by environmental allergens of Th2 cells in atopic subjects still remain obscure. Among the possibilities are alterations to molecular mechanisms directly involved in the regulation of IL-4 gene expression or deficient regulatory activity of cytokines that antagonize Th2 cells.
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PMID:Regulation of the development of type 2 T-helper cells in allergy. 771 Jul 7

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

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

We isolated cDNAs encoding a mouse interleukin 10 receptor (mIL-10R) from mouse mast cell and macrophage cell lines. The two cDNAs are substantially identical and express an approximately 110-kDa polypeptide in COS7 cells, which binds mIL-10 specifically. A mouse pro-B-cell line (Ba/F3) expressing transfected recombinant mIL-10R binds IL-10 with high affinity (approximately 70 pM) and proliferates in response to mIL-10. mIL-10R is structurally related to interferon receptors (IFNRs). Since IL-10 inhibits macrophage activation by IFN-gamma, a possible implication of this relationship interaction of IL-10R and IFN-gamma R or their signaling pathways.
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PMID:A receptor for interleukin 10 is related to interferon receptors. 824 39


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