Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An immunohistochemical technique was used to examine whether there was a colocalization of cytokine-specific receptors with cytokine-expressing cells. We have previously shown that there is extensive cytokine production and secretion in the rectal mucosa in shigellosis (interleukin 1 alpha [IL-1 alpha], IL-1 beta, IL-1ra, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha [TNF-alpha], TNF-beta, gamma interferon, granulocyte-macrophage colony-stimulating factor, and transforming growth factor beta [TGF-beta]) (R. Raqib, A. A. Lindberg, B. Wretlind, P. K. Bardhan, U. Andersson, and J. Andersson, Infect. Immun. 63:289-296, 1995; R. Raqib, B. Wretlind, J. Andersson, and A. A. Lindberg, J. Infect. Dis. 171:376-384, 1995). Kinetics for receptor expression was compared with that for cytokine synthesis in the inflamed rectal mucosa from Shigella-infected patients during acute (2 to 6 days after onset of diarrhea) and convalescent (30 to 40 days after onset) stages. Quantification of receptor expression was assessed by computer-assisted analysis of video microscopic images. A selective down-regulation of the receptors for gamma interferon, tumor necrosis factor (TNF receptor [TNFR] type I), IL-1 (IL-1 receptor [IL-1R] types I and type II), IL-3, IL-4, and TGF-beta (TGF-beta receptor type I) was observed at the onset of the disease, with a gradual reappearance during the convalescent stage. However, IL-2R, IL-6R, granulocyte-macrophage colony-stimulating factor receptor, TNFR type II, and TGF-beta receptor type II showed no change in expression during the study period and were comparable to controls. Cytokine receptors were predominantly located to the epithelial layer of the mucosal surface and crypts, with variable expression patterns in the lamina propria. A time-dependent kinetic curve was seen for the soluble IL-2R (sIL-2R), sIL-6R, and sTNFR types I and type II shed in stool at the acute stage similar to that observed for cytokine secretion in stool but at four- to six-times-lower concentration. In contrast, soluble receptor levels in plasma were 100-fold higher than the cytokine levels. The results suggest a dissociation in immune regulation between cytokine production and cytokine receptor expression. The down-regulation of the receptors in acute shigellosis was probably a consequence of cytokine-induced internalization and shedding of the receptors during signal transduction as well as due to programmed regulatory roles played by cytokines and the bacterial antigens.
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PMID:Down-regulation of gamma interferon, tumor necrosis factor type I, interleukin 1 (IL-1) type I, IL-3, IL-4, and transforming growth factor beta type I receptors at the local site during the acute phase of Shigella infection. 762 34

Topical administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) into the subcutaneous tissue or in the pulmonary alveoli of the rat induces a fibrotic reaction characterized by the presence of alpha-smooth muscle actin-rich myofibroblasts, suggesting that GM-CSF plays a role in the development of fibrotic changes. A high level of expression of GM-CSF also has been demonstrated in epidermal cells during human atopic dermatitis. It is accepted that transforming growth factor beta1 (TGF-beta1) plays a key role in the modulation from fibroblast into myofibroblast, although it is not known how TGF-beta1 activity is stimulated. Up until now, no evidence of early GM-CSF expression during development of fibrosis has been reported. Herein we have studied, using RT-competitive PCR, the expression of GM-CSF mRNA during the early steps of pulmonary fibrosis development after intra-alveolar instillation of bleomycin, a well-established experimental model of this lesion. GM-CSF mRNA was already increased in the total lung at 6 hours and maximal at 12 hours after bleomycin instillation and returned to basal levels at 24 hours. This was followed by an increase of TGF-beta1 and TGF-beta receptor type II (but not of types I and III) mRNAs. Analyses of macrophages and polymorphonuclear neutrophils isolated by bronchoalveolar lavage 12 hours after bleomycin instillation indicated that they were responsible, at least in part, for the accumulation of GM-CSF mRNA. Our results show for the first time that GM-CSF is expressed, very early and temporarily, by inflammatory cells accumulating in the alveolus after bleomycin administration and before the appearance of TGF-beta1. Moreover, we have shown that GM-CSF induces the expression of TGF-beta1 mRNA by alveolar macrophages. Our data support the possibility that GM-CSF participates in the initial steps of the chain of events leading to fibrosis, perhaps through a stimulation of TGF-beta1 production.
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PMID:Early granulocyte-macrophage colony-stimulating factor expression by alveolar inflammatory cells during bleomycin-induced rat lung fibrosis. 988 49