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pubmed-article:1505923pubmed:abstractTextDuring liver fibrogenesis, fat-storing cells transform into myofibroblast-like cells and produce increasing amounts of extracellular matrix proteins. Because fat-storing cells produce alpha 2-macroglobulin, an important serine protease inhibitor (serpin), we investigated whether fat-storing cells also synthesize C1-esterase inhibitor, another important serpin. C1-esterase inhibitor synthesis was studied in rat fat-storing cells at day 0, 3 and 7 after isolation by biosynthetic labeling, immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Messenger RNA was examined by Northern-blot analysis. C1-esterase inhibitor gene expression and synthesis were detectable in freshly isolated fat-storing cells and increased distinctly during the time in culture. The cellular source of C1-esterase inhibitor in fat-storing cell cultures was also identified by in situ hybridization of cells at different times after isolation. By inhibition of the N-glycosylation using tunicamycin, rat C1-esterase inhibitor was identified as a glycoprotein. The time course of C1-esterase inhibitor secretion was determined by pulse-chase experiments. C1-esterase inhibitor synthesis was increased 6-fold to 10-fold by interferon-gamma. Specific messenger RNA levels were also raised distinctly by this cytokine. In contrast, interferon-alpha and dexamethasone did not alter C1-esterase inhibitor gene expression. Because C1-esterase inhibitor synthesis is increased by advancing culture time and by the inflammatory mediator interferon-gamma, we suggest that fat-storing cells may enhance the deposition of extracellular matrix proteins by inhibiting their degradation.lld:pubmed
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pubmed-article:1505923pubmed:articleTitleFat-storing cells of the rat liver synthesize and secrete C1-esterase inhibitor; modulation by cytokines.lld:pubmed
pubmed-article:1505923pubmed:affiliationDepartment of Internal Medicine, University of Mainz, Germany.lld:pubmed
pubmed-article:1505923pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:1505923pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed