NDLI: 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

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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

Content Provider	Springer Nature Link
Author	Zheng, Yijie Luo, Naixiang Mu, Dongzhen Jiang, Pei Liu, Ronghua Sun, Haozhe Xiong, Shudao Liu, Xiaoming Wang, Luman Chu, Yiwei
Copyright Year	2013
Abstract	Hydrogen sulfide (H$_{2}$S), formed mainly by the enzyme cystathionine γ-lyase (CSE) in macrophages, is emerging as a novel regulator in inflammation. Although elevated production of H$_{2}$S 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 H$_{2}$S 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 H$_{2}$S. 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 H$_{2}$S 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 H$_{2}$S in macrophages mainly in a TLR4-p38-dependent and TLR-4-NF-κB-dependent manner. These findings expand our knowledge of H$_{2}$S biosynthesis during inflammation and provide a foundation for the development of novel H$_{2}$S-based therapies.
Starting Page	679
Ending Page	688
Page Count	10
File Format	PDF
ISSN	10712690
Journal	In Vitro Cellular & Developmental Biology - Animal
Volume Number	49
Issue Number	9
e-ISSN	1543706X
Language	English
Publisher	Springer US
Publisher Date	2013-07-23
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Hydrogen sulfide Cystathionine γ-lyase Lipopolysaccharide Nitric oxide Nuclear factor kappa B Cell Biology Developmental Biology Stem Cells Cell Culture Animal Genetics and Genomics
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Medicine

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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

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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

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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