Viral Hepatitis
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2005; 11(42): 6631-6637
Published online Nov 14, 2005. doi: 10.3748/wjg.v11.i42.6631
Toll-like receptor 4 plays an anti-HBV role in a murine model of acute hepatitis B virus expression
Wen-Wei Chang, Ih-Jen Su, Ming-Derg Lai, Wen-Tsan Chang, Wenya Huang, Huan-Yao Lei
Wen-Wei Chang, Institute of Basic Medical Science, National Cheng Kung University Medicine College, Tainan, Taiwan, China
Ih-Jen Su, Division of Clinical Research, National Health Research Institute, Tainan, Taiwan, China
Ming-Derg Lai, Wen-Tsan Chang, Department of Biochemistry, National Cheng Kung University Medicine College, Tainan, Taiwan, China
Wenya Huang, Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Medicine College, Tainan, Taiwan, China
Huan-Yao Lei, Department of Microbiology and Immunology, National Cheng Kung University Medicine College, Tainan, Taiwan, China
Author contributions: All authors contributed equally to the work.
Supported by grant form National Science Council of Taiwan, No. NSC 93-2320-B006-026
Correspondence to: Dr. Huan-Yao Lei, Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, China. hylei@mail.ncku.edu.tw
Telephone: +886-6-2353535 Ext. 5643 Fax: +886-6-2097825
Received: April 29, 2005
Revised: June 15, 2005
Accepted: June 18, 2005
Published online: November 14, 2005
Abstract

AIM: Toll-like receptor 4 (TLR4) has been shown to be important for bacterial infection, especially to lipopolysaccharide signaling. Its possible role in HBV infection is studied in the present study.

MATERIALS AND METHODS: pHBV3.6 plasmid, containing full-length HBV genome was used in the murine model of acute HBV expression by hydrodynamics in vivo transfection. TLR4 normal or mutant mouse strain was compared to investigate the possible role of TLR4 in acute HBV expression.

RESULTS: After pHBV3.6 injection, the infiltrating leukocytes expressed TLR4 were observed nearby the HBsAg-expressing hepatocytes. The HBV antigenemia as well as the replication and transcription were higher in TLR4-mutant C3H/HeJ mice than in normal C3H/HeN mice. The HBV-specific immune responses were impaired in the liver or spleen of the C3H/HeJ mice. Their inducible nitric oxide synthase (iNOS) expression on the hepatic infiltrating cells was also impaired. When adoptively transferring splenocytes from C3H/HeN mice to C3H/HeJ mice, the HBV replication was inhibited to the level as that of C3H/HeN.

CONCLUSION: These results suggest that TLR4 plays an anti-HBV role in vivo through the induction of iNOS expression and HBV-specific immune responses after HBV expression.

Keywords: TLR4, Rodent, HBV, iNOS, Liver