IL-6 stimulates vitronectin gene expression in vivo.
We tested the hypothesis that vitronectin (Vn) is regulated as an acute phase reactant in response to inflammatory stimuli. In initial experiments, Vn levels were measured during the surgically induced acute phase response in humans. The plasma concentration of Vn increased approximately twofold following elective orthopedic surgery and remained elevated up to 5 days. To examine the mechanism(s) of increased Vn synthesis, hepatic Vn mRNA expression and serum levels were examined in three rat models of acute inflammation: LPS (i.v.), CFA (i.p.), or turpentine (s.c.) injection. The serum concentration of Vn increased approximately twofold 24 h following treatment with turpentine. The expression of Vn mRNA in the liver increased markedly as early as 3 h after treatment in these models and remained elevated up to 18 h. Northern blot analysis of RNA isolated from fractionated liver cells derived from rats treated with LPS indicated that Vn was mainly expressed in hepatocytes, but not in the endothelial or nonparenchymal cell fractions. To analyze the individual effects of raised corticosterone and IL-6 levels on the expression of hepatic Vn mRNA, rats were injected (i.p.) with either dexamethasone or purified recombinant rat IL-6. Vn mRNA expression was elevated within 1 h after IL-6 injection, whereas dexamethasone-injected rats showed unchanged Vn expression. Vn mRNA also was increased in rats chronically injected with IL-6. These results indicate that the Vn gene is up-regulated in acute and chronic inflammation, and this induction is primarily mediated by IL-6.
Seiffert
D
D
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Geisterfer
M
M
Gauldie
J
J
Young
E
E
Podor
T J
TJ
D000818:Animals; D006023:Glycoproteins / Q000032:analysis* / Q000097:blood / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008099:Liver / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014425:Turpentine; D019096:Vitronectin
D006023:Glycoproteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019096:Vitronectin; D014425:Turpentine