Regulation of fibrinogen biosynthesis: glucocorticoid and interleukin-6 control.
Fibrinogen biosynthesis is regulated under normal and pathophysiological conditions by the constitutive, hormonal and cytokine-mediated mechanisms. As an acute-phase protein, fibrinogen biosynthesis is regulated by glucocorticoids and cytokines. Recent studies have defined glucocorticoid-consensus sequences on the beta-chain promoter. The cytokine mediating production of fibrinogen, originally termed leukocyte endogenous mediator and hepatocyte stimulatory factor, has now been demonstrated to be derived from a single gene family of cytokines called interleukin-6 (IL-6). IL-6 forms produced by mammalian fibroblasts, T-cells and endothelial cells, as well as monocytic cells, can stimulate basal levels of fibrinogen production in vitro and in vivo. Studies carried out in mammalian hepatocyte systems, with natural or recombinant IL-6, show a dependency on the presence of glucocorticoids to provide a maximal effect. Our results demonstrated the ability of purified human recombinant interleukin-6 (originally BSF-2) to stimulate fibrinogen production in primary chicken hepatocytes in a dose-dependent manner. Conditioned medium from primary chick fibroblasts unstimulated or stimulated with purified natural interleukin-1 (IL-1), induced a dose-dependent increase in fibrinogen levels in cultured chick hepatocytes. IL-1 alone had little or no direct effect on fibrinogen production.
Amrani
D L
DL
University of Wisconsin-Milwaukee, Department of Health Sciences 53201.
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D005340:Fibrinogen / Q000096:biosynthesis* / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008322:Mammals / Q000378:metabolism
D005938:Glucocorticoids; D015850:Interleukin-6; D005340:Fibrinogen