Lipopolysaccharide regulates biosynthesis of cystathionine γ-lyase and hydrogen sulfide through Toll-like receptor-4/p38 and Toll-like receptor-4/NF-κB pathways in macrophages

Yijie Zheng; Naixiang Luo; Dongzhen Mu; Pei Jiang; Ronghua Liu; Haozhe Sun; Shudao Xiong; Xiaoming Liu; Luman Wang; Yiwei Chu

doi:10.1007/s11626-013-9659-4

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Lipopolysaccharide regulates biosynthesis of cystathionine γ-lyase and hydrogen sulfide through Toll-like receptor-4/p38 and Toll-like receptor-4/NF-κB pathways in macrophages

Journal article

Peer reviewed

Lipopolysaccharide regulates biosynthesis of cystathionine γ-lyase and hydrogen sulfide through Toll-like receptor-4/p38 and Toll-like receptor-4/NF-κB pathways in macrophages

Yijie Zheng, Naixiang Luo, Dongzhen Mu, Pei Jiang, Ronghua Liu, Haozhe Sun, Shudao Xiong, Xiaoming Liu, Luman Wang and Yiwei Chu

In vitro cellular & developmental biology. Animal, Vol.49(9), pp.679-688

10/2013

DOI: 10.1007/s11626-013-9659-4

PMID: 23877364

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Abstract

Hydrogen sulfide (H2S), formed mainly by the enzyme cystathionine γ-lyase (CSE) in macrophages, is emerging as a novel regulator in inflammation. Although elevated production of H2S has been shown in inflammatory processes, the underlying molecular mechanism remains to be further elucidated. In this study, we compared parallel TLR4 knockout (TLR4(-/-)) mice with their wild-type counterparts following lipopolysaccharide (LPS) treatment. It showed that LPS increased the expressions of CSE and biosynthesis of H2S in C57BL/6 mice both in vivo and in vitro. However, the effects of LPS were not present in TLR4(-/-) mice, indicating the crucial role of TLR4 in LPS-induced expression of CSE and biosynthesis of H2S. We subsequently used JNK inhibitor, P38 inhibitor, and ERK inhibitor to block the downstream MAPK pathways of TLR4 in macrophages, and found that LPS-induced CSE expression and H2S synthesizing activity were inhibited by pretreatment with the p38 inhibitor. Similarly, the NF-κB inhibitor (BAY 11-7082) reversed the effects of LPS. These results suggest that LPS increases the biosynthesis of CSE and H2S in macrophages mainly in a TLR4-p38-dependent and TLR-4-NF-κB-dependent manner. These findings expand our knowledge of H2S biosynthesis during inflammation and provide a foundation for the development of novel H2S-based therapies.

Animals

Cystathionine gamma-Lyase - biosynthesis

Gene Expression Regulation - drug effects

Humans

Hydrogen Sulfide - metabolism

Lipopolysaccharides - toxicity

Macrophages - metabolism

MAP Kinase Signaling System - drug effects

MAP Kinase Signaling System - genetics

Mice

Mice, Knockout

NF-kappa B - genetics

NF-kappa B - metabolism

Toll-Like Receptor 4 - genetics

Toll-Like Receptor 4 - metabolism

Details

Title: Subtitle: Lipopolysaccharide regulates biosynthesis of cystathionine γ-lyase and hydrogen sulfide through Toll-like receptor-4/p38 and Toll-like receptor-4/NF-κB pathways in macrophages
Creators: Yijie Zheng - Fudan University
Naixiang Luo
Dongzhen Mu
Pei Jiang
Ronghua Liu
Haozhe Sun
Shudao Xiong
Xiaoming Liu
Luman Wang
Yiwei Chu
Resource Type: Journal article
Publication Details: In vitro cellular & developmental biology. Animal, Vol.49(9), pp.679-688
DOI: 10.1007/s11626-013-9659-4
PMID: 23877364
ISSN: 1071-2690
eISSN: 1543-706X
Language: English
Date published: 10/2013
Academic Unit: Anatomy and Cell Biology
Record Identifier: 9984288793202771

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