IL-6 STIMULATES VITRONECTIN GENE-EXPRESSION IN-VIVO

We tested the hypothesis that vitronectin (Vn) is regulated as an acut e phase reactant in response to inflammatory stimuli, In initial exper iments, Vn levels were measured during the surgically induced acute ph ase response in humans. The plasma concentration of Vn increased appro ximately twofold following elective orthopedic surgery and remained el evated up to 5 days. To examine the mechanism(s) of increased Vn synth esis, hepatic Vn mRNA expression and serum levels were examined in thr ee rat models of acute inflammation: LPS (i.v.), CFA (i.p.), or turpen tine (s.c.) injection. The serum concentration of Vn increased approxi mately twofold 24 h following treatment with turpentine. The expressio n of Vn mRNA in the liver increased markedly as early as 3 h after tre atment in these models and remained elevated up to 18 h. Northern blot analysis of RNA isolated from fractionated liver cells derived from r ats treated with LPS indicated that Vn was mainly expressed in hepatoc ytes, but not in the endothelial or nonparenchymal cell fractions. To analyze the individual effects of raised corticosterone and IL-6 level s on the expression of hepatic Vn mRNA, rats were injected (i.p.) with either dexamethasone or purified recombinant rat IL-6. Vn mRNA expres sion was elevated within 1 h after IL-6 injection, whereas dexamethaso ne-injected rats showed unchanged Vn expression, Vn mRNA also was incr eased in rats chronically injected with IL-6. These results indicate t hat the Vn gene is up-regulated in acute and chronic inflammation, and this induction is primarily mediated by IL-6.