Functional roles of CCL5/RANTES in liver disease

Abstract

Inflammation, which is mediated by leukocyte trafficking and activation, plays a prominent role in the pathogenesis of acute and chronic liver injury. Chemokines are critical mediators involved in the migration of leukocytes into the diseased liver via binding to their G protein-coupled receptors. C–C motif ligand 5 (CCL5) belongs to the CC-chemokine family and is secreted by several hepatic cell populations including hepatocytes, macrophages, hepatic stellate cells, and endothelial cells upon activation. CCL5 regulates the recruitment and migration of T cells (via CCR5) and NK cells (via CCR1). Moreover, CCL5 activates and stimulates T cell proliferation and cytokine production, sequentially regulating inflammatory responses. Accumulating studies have identified crucial effects of CCL5 both in liver-disease patients and in experimental models, in which CCL5 is elevated and displays distinct effects according to pathological conditions. In this review, we discussed the crucial functions of CCL5 in liver diseases, including acute liver failure, hepatic ischemia-reperfusion injury, acute liver failure, acute and viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, fibrosis, and hepatocellular carcinoma. Continued understanding the roles of CCL5 in liver disease and their mechanisms of activation are indispensable for the development of effective clinical therapeutics. Keywords: C-C motif ligand 5 (CCL5), Chemokines, Liver injury, Hepatitis, Alcoholic liver disease (ALD), Non-alcoholic fatty liver disease (NAFLD), Fibrosis, Hepatocellular carcinoma (HCC)