NutritionInflammatory Molecules Promote Liver Scarring
Scarring of the liver, which can progress to cirrhosis and/or cancer of the liver, is caused by persistent liver damage, such as occurs in those with untreated hepatitis C or alcoholism. Although such scarring (fibrosis) develops in an inflammatory environment, the role of inflammatory molecules has not been well defined. However, a team of researchers at Columbia University, New York, and UCSD, La Jolla, has established that the proteins CCR1 and CCR5 and the soluble inflammatory molecules that bind to them promote the development of liver fibrosis in mice.
The team, led by Robert Schwabe and Ekihiro Seki, observed that expression of the inflammatory molecules MIP-1-alpha, MIP-1-beta, and RANTES, and the proteins to which they bind (CCR1 and CCR5), was increased in 2 mouse models of liver fibrosis. Consistent with a role for these molecules in the development of liver fibrosis, preventing the inflammatory molecules binding CCR1 and CCR5 reduced liver fibrosis, as did eliminating expression of either CCR1 or CCR5. The latter experiments also identified the cells on which CCR1 and CCR5 expression is important for promoting liver fibrosis. As expression of RANTES, CCR1, and CCR5 was detected in the livers of patients with cirrhosis, the authors suggest that targeting CCR1 and CCR5 (for which there are already small molecule inhibitors in clinical development) might be a viable approach to prevent liver fibrosis.
TITLE: CCR1 and CCR5 promote hepatic fibrosis in mice
AUTHORS:
Robert F. Schwabe
Columbia University, New York, New York, USA.
Ekihiro Seki
University of California, San Diego, La Jolla, California, USA.
View the PDF of this article at: https://www.the-jci.org/article.php?id=37444
Karen Honey
Journal of Clinical Investigation
JCI online early table of contents: June 15, 2009