Basic Research
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 15, 2003; 9(8): 1799-1803
Published online Aug 15, 2003. doi: 10.3748/wjg.v9.i8.1799
TLR4 mediates LPS-induced HO-1 expression in mouse liver: Role of TNF-α and IL-1β
Yong Song, Yi Shi, Li-Hua Ao, Alden H. Harken, Xian-Zhong Meng
Yong Song, Yi Shi, Department of Respiratory Diseases, Nanjing Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, China
Li-Hua Ao, Alden H. Harken, Xian-Zhong Meng, Department of Surgery, Box C-320, Health Sciences Center, University of Colorado, 4200 E. 9th Avenue, Denver, CO 80262, USA
Author contributions: All authors contributed equally to the work.
Correspondence to: Yong Song, M.D., Ph D., Department of Respiratory Diseases, Nanjing Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, China. yong_song6310@yahoo.com
Telephone: +86-25-4810453 Fax: +86-25-4809843
Received: January 18, 2003
Revised: January 21, 2003
Accepted: March 3, 2003
Published online: August 15, 2003
Abstract

AIM: Heme oxygenase (HO)-1 catalyzes the conversion of heme to biliverdin, iron and carbon monoxide. HO-1 is induced by many stimuli including heme, Hb, heat stress, lipopolysaccharide (LPS) and cytokines. Previous studies demonstrated that LPS induced HO-1 gene activation and HO-1 expression in liver. However, the mechanisms of LPS-induced HO-1 expression in liver remain unknown. The effect of toll-like receptor-4 (TLR4) on LPS-induced liver HO-1 expression and the role of TNF-α and IL-1β in this condition were determined.

METHODS: HO- 1 expression was determined by immunofluorescent staining and immunoblotting. Double immunofluorescent staining was performed to determine the cell type of HO-1 expression in liver.

RESULTS: A low dose of LPS significantly increased HO-1 expression in the liver which was localized in Kupffer cells only. Furthermore, HO-1 expression was enhanced by three doses of LPS. HO-1 expression was significantly inhibited in the liver of TLR4 mutant mice. While the liver HO-1 expression in TNF KO mice was much lower than that in C57 mice following the same LPS treatment, IL-1β KO had a slight influence on liver HO-1 expression following LPS treatment.

CONCLUSION: The present results confirm that macrophages are the major source of HO-1 in the liver induced by LPS. This study demonstrates that TLR4 plays a dominant role in mediating HO-1 expression following LPS. LPS-induced HO-1 expression is mainly mediated by endogenous TNF-α, but only partially by endogenous IL-1β.

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