Chemokine (CC-motif) receptor-like 2 mRNA is expressed in hepatic stellate cells and is positively associated with characteristics of non-alcoholic steatohepatitis in mice and men

Abstract

Chemokine (CC-motif) receptor-like 2 (CCRL2) is a decoy receptor and regulates the local responses of the chemokine chemerin. Recently our group has shown that the functional chemerin receptor, chemokine-like receptor 1 (CMKLR1), correlates with fibrosis and non-alcoholic steatohepatitis (NASH) score in males only. In our current study, we wanted to know whether CCRL2 shows similar correlations as CMKLR1. Therefore, we analyzed the hepatic expression of CCRL2 in murine NASH and in liver tissues obtained from 85 patients with non-alcoholic fatty liver disease (NAFLD) and 33 controls. CCRL2 mRNA was not significantly changed in murine and human NASH liver. CCRL2 mRNA levels were positively correlated with inflammation, fibrosis and NASH scores in the patients. Concordantly, CCRL2 was related to the mRNA levels of F4/80, transforming growth factor beta and alpha smooth muscle actin in murine NASH. In the human cohort, CCRL2 mRNA correlated with fibrosis score and CMKLR1 mRNA in both gender. CCRL2 mRNA was induced in the liver of type 2 diabetes and hypercholesterolemic patients, but still positively correlated with fibrosis score when these patients were excluded from calculations. Human hepatic stellate cells (HSC), hepatic sinusoidal endothelial cells and Kupffer cells (KC) express CCRL2 mRNA. TNF induces CCRL2 expression in HSC and lipopolysaccharide in KC suggesting that correlations identified in NAFLD patients are partly related to the activation of these cells.