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)

Leukemia inhibitory factor (LIF) is a pluripotent cytokine of importance in the regulation of immune and inflammatory responses. This cytokine may play an important role in neuronal development and bone metabolism. We have examined the ability of freshly isolated rat mast cells and mast cell lines to produce LIF at both the mRNA and bioactivity levels. Initial experiments demonstrated that two mucosal mast cell-like cell lines RBL.2H3 and RCMC9 endogenously produced low levels of LIF bioactivity. The production of this cytokine was examined using a hepatocyte-stimulating factor activity assay and confirmed by the use of neutralizing antibodies specific for LIF. This production was enhanced by treatment with the calcium ionophore A23187. No interleukin-6 production was observed by these cells either endogenously or following ionophore activation. Freshly isolated highly purified rat peritoneal mast cells also expressed mRNA for LIF. These results could have important implications for the role of mast cells in neuronal development, hematopoiesis bone metabolism and the acute-phase response.
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PMID:Leukemia inhibitory factor production by rat mast cells. 837 Mar 94

Leukemia inhibitory factor (LIF) is a cytokine involved in hematopoiesis, neuropoiesis, and embryogenesis. Transcriptional activation of various genes occurs subsequent to LIF signal transduction in its target cells. Using the mRNA differential display method, a LIF-inducible gene was isolated from LIF-stimulated M1 murine myeloid leukemia cells. By DNA sequencing, this gene turned out to be gp49B1, which has been reported as an inhibitory signaling receptor to attenuate mast cell activation. Because gp49B1 expression was limited to the uterus of a pregnant mouse, its uterine expression was examined especially in relation to LIF expression during pregnancy. gp49B1 was expressed specifically on day 4.0 of pregnancy, as was LIF, and the site of the most abundant expression of LIF and gp49B1 mRNA was the luminal epithelium of the uterine endometrium. These findings suggest that the gp49B1 expression in the uterine endometrium is induced just before implantation by paracrine and/or autocrine effects of LIF. Considering its function as an inhibitory signaling receptor on mast cells, a possible role for gp49B1 on the surface of the uterine endometrium as an immunoreceptor that allows blastocyst attachment is proposed.
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PMID:gp49B1, an inhibitory signaling receptor gene of hematopoietic cells, is induced by leukemia inhibitory factor in the uterine endometrium just before implantation. 933 94

Leukemia inhibitory factor (LIF) enhanced mast cell growth in a mast cell/3T3 fibroblast co-culture system, however the precise mechanisms have not been defined. Western blot analysis showed that bone marrow-derived mast cells failed to express both LIF receptor (LIFR) and gp130, whereas 3T3 fibroblasts expressed both LIFR and gp130. This result indicates that the activity of LIF for mast cell growth is mediated by 3T3 fibroblasts. Signal transducer and activator of transcription (Stat) 3-transfected 3T3 fibroblasts enhanced mast cell growth. In addition, dominant-negative Stat3-transfected fibroblasts blocked LIF-mediated mast cell growth in the co-culture system. In conclusion, LIF-induced mast cell growth in the co-culture system is mediated by an indirect pathway via 3T3 fibroblasts through activating Stat3 signaling pathway in 3T3 fibroblasts.
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PMID:Leukemia inhibitory factor enhances mast cell growth in a mast cell/fibroblast co-culture system through stat3 signaling pathway of fibroblasts. 1115 May 13

Inoculation of KCMH-1 cells, a keratinocyte-derived cell line established from a chemically induced skin tumor, into the skin of mice results in accumulation of mast cells around the resulting tumors. The conditioned medium of KCMH-1 cells enhances the growth of mast cells in vitro when they are cultured in the presence of NIH/3T3 fibroblasts, suggesting an important role for keratinocytes in mast cell hyperplasia in the skin. The aim of this study was to identify this mast cell growth-enhancing factor (MCGEF) by screening a KCMH-1 cDNA library. We first established a polyclonal antibody raised against the partially purified factor obtained from KCMH-1-conditioned medium which neutralized the MCGEF activity in KCMH-1-conditioned medium. Expression cloning of 1 x 10(6) cDNAs from the KCMH-1 cDNA library led to 16 cDNAs. One of these cloned cDNAs was found to be leukemia inhibitory factor (LIF). Both LIF produced by COS cells and the recombinant protein obtained commercially showed MCGEF activity when added to mast cell/fibroblast cocultures. MCGEF activity in KCMH-1-conditioned medium was completely neutralized by an anti-LIF monoclonal antibody. These results suggest that MCGEF produced by KCMH-1 cells is identical to LIF.
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PMID:Identification of leukemia inhibitory factor as a potent mast cell growth-enhancing factor produced by mouse keratinocyte cell line, KCMH-1. 1128 77

Mast cell hyperplasia is observed in various inflammatory skin diseases. Although the mechanisms involved in the pathogenesis of these conditions remains largely uninvestigated, it is speculated that mediators produced in the lesional skin provide a favorable microenvironment for mast cell growth. Among the proinflammatory mediators, leukemia inhibitory factor (LIF), which shares a receptor component (gp130 subunit) with interleukin-6 (IL-6), has been identified as a mast cell growth-enhancing factor produced by cells of the keratinocyte-derived cell line (KCMH-1). In this study, we investigated the effect of four IL-6 family cytokines, IL-6, IL-11, oncostatin M (OSM) and LIF on mast cell growth in a mast cell/fibroblast co-culture system. When mouse bone marrow-derived cultured mast cells (BMMC) were maintained on a NIH/3T3 fibroblast monolayer, these cytokines induced proliferation of the mast cells, but none of the cytokines had any effect on mast cell proliferation in the absence of fibroblasts. mRNA for gp130 and receptors for the four IL-6 family cytokines were detected in NIH/3T3 fibroblasts by reverse transcriptase-mediated polymerase chain reaction. In contrast, only mRNA for the IL-11 receptor and gp130 were detected in BMMC. Tyrosine phosphorylation of gp130 was observed in NIH/3T3 fibroblasts after stimulation with all the cytokines. Some IL-6 family cytokines enhanced the production of stem cell factor (SCF), a potent mast cell growth factor, from NIH/3T3 fibroblasts, but the amount of SCF produced by NIH/3T3 fibroblasts was not paralleled by the mast cell growth-enhancement induced by the IL-6 family cytokines. When anti-SCF antibody was added with the IL-6 family cytokines in the BMMC/fibroblast coculture system, a significant effect of these cytokines remained, although the growth-enhancing activity was markedly reduced. A similar result was obtained when BMMC were prepared from W/W(V)-mice, which lack functional c-kit, in the BMMC/ fibroblast coculture system. These results suggest that IL-6 family cytokines stimulate mast cell growth by a fibroblast-dependent mechanism, and also suggest the existence of another pathway between BMMC and NIH/3T3 fibroblasts cooperating with the SCF/c-kit pathway. IL-6 family cytokines may thus contribute to mast cell hyperplasia in skin diseases.
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PMID:The IL-6 family cytokines, interleukin-6, interleukin-11, oncostatin M, and leukemia inhibitory factor, enhance mast cell growth through fibroblast-dependent pathway in mice. 1182 Jul 27

Airway smooth muscle cells (ASMC) play a major role in airway inflammation, hyperresponsiveness, and obstruction in asthma. However, very little is known regarding the relation between inflammatory mediators and cytokines and immature ASMC. The aim of this study was to evaluate 1) the secretion of leukemia inhibitory factor (LIF) (an IL-6 family neurotrophic cytokine) by ASMC; 2) intracellular calcium concentration ([Ca(2+)](i)) signaling; and 3) the effect of LIF on mast cell chemotaxis and rat airway contractility. Immature and adult human ASMC were cultured. ELISA and real-time PCR were performed to assess LIF protein secretion and mRNA production, [methyl-(3)H]thymidine incorporation to quantify ASMC DNA synthesis, a Boyden chamber to evaluate the effect of LIF on mast cell chemotaxis, microspectroflurimetry using indo-1 (at baseline and after stimulation bradykinin, U-46619, histamine, and acetylcholine, in the presence or absence of LIF or TNF-alpha) for [Ca(2+)](i) signaling, and isolated rat pup tracheae to determine the effect of LIF on airway contractility to ACh. TNF-alpha-stimulated immature ASMC produce more LIF mRNA and protein than adult ASMC, although this cytokine induces a moderate increase in DNA synthesis (+20%) in adult ASMC only. Human recombinant LIF exerts no chemotactic effect on human mast cells. In immature ASMC, ACh-induced [Ca(2+)](i) response was enhanced twofold after incubation with LIF, whereas TNF-alpha increased the [Ca(2+)](i) to U-46619 threefold. In TNF-alpha-exposed adult ASMC, [Ca(2+)](i) responses to ACh were of greater magnitude (sixfold increase) than in immature ASMC. Human recombinant LIF increased contractility to ACh by 50% in immature, isolated rat tracheae. Stimulated immature human ASMC greatly secrete LIF, thus potentially contributing to neuroimmune airway inflammation and subsequent remodeling. Increased LIF secretion enhances airway reactivity and [Ca(2+)](i) signaling.
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PMID:Increased secretion of leukemia inhibitory factor by immature airway smooth muscle cells enhances intracellular signaling and airway contractility. 1648 16