Hepatic expression of toll-like receptors 3, 4, and 9 in primary biliary cirrhosis and chronic hepatitis C

Toll-like receptors (TLRs) may play a role in the inflammatory patterns observed in primary biliary cirrhosis (PBC) and chronic hepatitis C (CHC). We investigated TLR 3, 4 and 9 expression in PBC and CHC using immunohistochemical staining. Methods: Patient biopsies of PBC (N = 11) and CHC (N = 15) were compared to disease free livers (n = 7). The extent of TLR staining was assessed separately according to a semi-quantitative scale for hepatocytes, cholangiocytes and portal mononuclear cells (PMC). Results: In hepatocytes, TLR4 expression was increased (PBC; P = 0.019), as was TLR9 (PBC; P = 0.006, CHC; P = 0.001). Cholangiocyte expression of TLRs 4 and 3 was reduced in both PBC (TLR4; P < 0.0001, TLR3; P = 0.006) and CHC (TLR4; P < 0.0001, TLR3; P = 0.014). Cholangiocyte expression of TLR9 was elevated for both groups and was significant in CHC (P = 0.0115). PMCs showed up-regulation of TLR9 in PBC (P = 0.022) and CHC (P = 0.0001), with almost no expression of TLR 3 or 4. Conclusions: In PBC and CHC, hepatocytes showed increased TLR 4 and 9 expression without change in TLR3. Cholangiocytes showed increased TLR9 expression as opposed to down-regulation of TLRs 3 and 4. PMCs in both diseases had significantly increased TLR 9 expression perhaps implicating TLR9 expression in chronic liver inflammation. (c) 2012 Elsevier Masson SAS. All rights reserved.