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Cellular and Molecular Life Sciences

, Volume 67, Issue 7, pp 1119–1132 | Cite as

Glucocorticoids suppress cystathionine gamma-lyase expression and H2S production in lipopolysaccharide-treated macrophages

  • Xiao-Yan Zhu
  • Shu-Juan Liu
  • Yu-Jian Liu
  • Shan Wang
  • Xin Ni
Research Article

Abstract

Hydrogen sulfide (H2S) plays an important role in inflammation. We showed that macrophages expressed the H2S-forming enzyme cystathionine gamma-lyase (CSE) and produced H2S. Lipopolysaccharide (LPS) stimulated the CSE expression and H2S production rate. l-cysteine reduced LPS-induced nitric oxide (NO) production. CSE inhibitor blocked the inhibitory effect of l-cysteine. CSE knockdown increased, whereas CSE overexpression decreased LPS-induced NO production. Dexamethasone suppressed LPS-induced CSE expression and the H2S production rate as well as NO production. l-arginine increased, whereas NG-nitro-l-arginine methyl ester (l-NAME) decreased LPS-induced CSE expression and H2S production. Dexamethasone plus l-NAME significantly decreased LPS-induced CSE expression and H2S production compared to l-NAME. Our results suggest that macrophages are one of the H2S producing sources. H2S might exert anti-inflammatory effects by inhibiting NO production. Dexamethasone may directly inhibit CSE expression and H2S production, besides the NO-dependent way. Inhibition of H2S and NO production may be a mechanism by which glucocorticoids coordinate the balance between pro- and anti-inflammatory mediators during inflammation.

Keywords

Glucocorticoids Hydrogen sulfide Cystathionine γ-lyase Lipopolysaccharide Macrophages 

Abbreviations

H2S

Hydrogen sulfide

NO

Nitric oxide

CO

Carbon monoxide

CSE

Cystathionine gamma-lyase

CBS

Cystathionine β-synthetase

fMLP

Formyl-methionyl-leucyl-phenylalanine

TNF-α

Tumor necrosis factor-α

GCs

Glucocorticoids

GR

Glucocorticoid receptor

MIF

Migration inhibitory factor

LPS

Lipopolysaccharide

IL-1

Interleukin-1

IL-6

Interleukin-6

MTT

3-[4, 5-Dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide

PAG

dl-propargylglycine

l-NAME

NG-nitro-l-arginine methyl ester

iNOS

Inducible nitric oxide synthase

CD-FBS

Charcoal-stripped FBS

PLP

Pyridoxal-5′-phosphate

siRNA

Interfering RNA

RAW-EGFP-mCSE

CSE-overexpression RAW264.7 cell lines

RAW-mCSE siRNA

CSE-knockdown RAW264.7 cell lines

TBST

Tris-buffered saline/Tween 20

Notes

Acknowledgments

The authors wish to thank Dr. I.Ishii, Gunma University Graduate School of Medicine, Gunma, Japan, for his gift of pCSE-PGL3 plasmid. This work was supported by the National Natural Science Foundation of China, grant nos. 30670815 and 30770846, and the Science and Technology Commission of Shanghai Municipals (09XD1405600).

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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2010

Authors and Affiliations

  • Xiao-Yan Zhu
    • 1
    • 3
  • Shu-Juan Liu
    • 1
    • 3
  • Yu-Jian Liu
    • 2
  • Shan Wang
    • 1
    • 3
  • Xin Ni
    • 1
    • 3
  1. 1.Department of PhysiologySecond Military Medical UniversityShanghaiPeople’s Republic of China
  2. 2.Department of PathophysiologySecond Military Medical UniversityShanghaiPeople’s Republic of China
  3. 3.Key Laboratory Neurobiology, Ministry of EducationSecond Military Medical UniversityShanghaiPeople’s Republic of China

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