Expression of monocyte chemotactic protein-1 precedes monocyte recruitmentin a rat model of acute liver injury, and is modulated by vitamin E

Background: Increased expression of monocyte chemotactic protein-1 (MCP-1) has been indicated as a mechanism underlying leukocyte recruitment after li ver injury. In this study we examined the temporal relationship between MCP -1 expression and the appearance of monocyte infiltration during acute live r injury. In addition, we tested the effects of vitamin E, a well known ant ioxidant, on these parameters. Rats were intoxicated with a single intragas tric administration of CCl4 with or without pretreatment with vitamin E (a- tocopherol), Methods: Monocyte chemotactic protein-1 expression was analyzed by northern blotting and in situ hybridization and monocyte infiltration was determine d by ED-1 immunostaining. The results were quantitated by computerized imag e analysis. Expression of MCP-1 mRNA was significantly increased as early a s 12 hours following injury, and progressively increased thereafter, In con trast, a significant increase in the number of ED-1 positive cells, an inde x of monocyte infiltration, was observed only 24 and 48 hours after injury. Results: Vitamin E markedly reduced MCP-1 expression at the mRNA and prote in levels, and caused a significant reduction in the number of monocyte/mac rophages, indicating a role for oxidative stress in the induction of MCP-1 expression in vivo, Accordingly, in cultured hepatic stellate cells, differ ent oxidative stress-related molecules increased MCP-I mRNA, Conclusions: These data suggest the existence of a direct relationship betw een MCP-1 expression and monocyte infiltration after acute liver injury, an d that preventing the generation of oxidative stress-related molecules resu lts in decreased expression and release of this chemokine.