Fat-storing cells of the rat liver synthesize and secrete C1-esterase inhibitor; modulation by cytokines.
During 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.
Schwögler
S
S
Department of Internal Medicine, University of Mainz, Germany.
Odenthal
M
M
Knittel
T
T
Meyer zum Büschenfelde
K H
KH
Ramadori
G
G
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015854:Up-Regulation / Q000187:drug effects*
D003174:Complement C1 Inactivator Proteins; D012333:RNA, Messenger; D003907:Dexamethasone; D007371:Interferon-gamma