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

• Published in: Journal of investigative medicine Vol. 47; no. 1; p. 66
• Main Authors: Marra, F, DeFranco, R, Grappone, C, Parola, M, Milani, S, Leonarduzzi, G, Pastacaldi, S, Wenzel, U O, Pinzani, M, Dianzani, M U, Laffi, G, Gentilini, P
• Format: Journal Article
• Language: English
• Published: England 01.01.1999
• Subjects: Animals; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - genetics; Chemotaxis, Leukocyte; Gene Expression - drug effects; Humans; Liver - injuries; Liver - metabolism; Liver - pathology; Male; Monocytes - pathology; Monocytes - physiology; Rats; Rats, Wistar; RNA, Messenger - genetics; RNA, Messenger - metabolism; Vitamin E - pharmacology
• ISSN: 1081-5589

Increased expression of monocyte chemotactic protein-1 (MCP-1) has been indicated as a mechanism underlying leukocyte recruitment after liver injury. In this study we examined the temporal relationship between MCP-1 expression and the appearance of monocyte infiltration during acute liver injury. In addition, we tested the effects of vitamin E, a well known antioxidant, on these parameters. Rats were intoxicated with a single intragastric administration of CCl4 with or without pretreatment with vitamin E (atocopherol). Monocyte chemotactic protein-1 expression was analyzed by northern blotting and in situ hybridization and monocyte infiltration was determined by ED-1 immunostaining. The results were quantitated by computerized image analysis. Expression of MCP-1 mRNA was significantly increased as early as 12 hours following injury, and progressively increased thereafter. In contrast, a significant increase in the number of ED-1 positive cells, an index of monocyte infiltration, was observed only 24 and 48 hours after injury. Vitamin E markedly reduced MCP-1 expression at the mRNA and protein levels, and caused a significant reduction in the number of monocyte/macrophages, indicating a role for oxidative stress in the induction of MCP-1 expression in vivo. Accordingly, in cultured hepatic stellate cells, different oxidative stress-related molecules increased MCP-1 mRNA. These data suggest the existence of a direct relationship between MCP-1 expression and monocyte infiltration after acute liver injury, and that preventing the generation of oxidative stress-related molecules results in decreased expression and release of this chemokine.