Downregulation of TIPE2 mRNA expression in peripheral blood mononuclear cells from patients with chronic hepatitis C

Abstract

Purpose: Hepatitis C virus (HCV) infection causes chronic hepatitis in approximately 80 % of cases. Although it is well recognized that the immune system plays an important role in determining the outcomes of HCV infection, the underlying molecular mechanisms of persistent HCV infection and hepatic injury are incompletely understood. Tumor necrosis factor-α-induced protein 8-like 2 (TNFAIP8L2, TIPE2) is a newly identified negative regulator of innate and adaptive immunity. The goal of the present study is to investigate the potential role of TIPE2 in chronic hepatitis C (CHC) infection.

Methods: We used quantitative real-time reverse transcription polymerase chain reaction to examine the mRNA expression levels of TIPE2, Toll-like receptor (TLR) 2, and TLR4 in peripheral blood mononuclear cells from 60 CHC patients and 30 healthy controls.

Results: The TIPE2 mRNA expression was significantly downregulated, whereas that of TLR2 and TLR4 was upregulated in CHC patients compared with healthy controls. TIPE2 mRNA expression levels were negatively correlated with serum ALT, AST, and HCV RNA levels. TIPE2 mRNA expression was also negatively correlated with TLR2 and TLR4 mRNA levels in CHC patients. Moreover, TIPE2 mRNA expression was upregulated, whereas that of TLR2 and TLR4 was downregulated after treatment of patients with interferon-α and ribavirin.

Conclusions: These results indicate that HCV may promote chronic hepatitis by decreasing TIPE2 expression while enhancing TLR signaling.

Keywords: Chronic hepatitis C; TLR2; TLR4; TNFAIP8L2.