Cytokine blockade inhibits hepatic TIMP-1 expression and upregulates MMP-9 in toxic liver injury

Aims: TIMP-1, the most important endogenous inhibitor of many matrix metalloproteinases, plays an important role in the pathogenesis of liver fibrosis and may represent an effective therapeutic target in the design of anti-fibrotic strategies for ch ronic liver disease. Male Sprague-Dawley rats were treated with CCl4 in the presence and absence of specific cytokine inhibitors. Methods and Results: Toxic liver injury was induced by a single intraperitoneal injection of CCl4. Real time PCR revealed a significant increase (to 627±354%, p=0.006) of TIMP-1 mRNA in total rat liver 24h after CCl4 injection. TNFa and IL…