Glucocorticoids suppress cystathionine gamma-lyase expression and H2S production in lipopolysaccharide-treated macrophages.
Hydrogen sulfide (H(2)S) plays an important role in inflammation. We showed that macrophages expressed the H(2)S-forming enzyme cystathionine gamma-lyase (CSE) and produced H(2)S. Lipopolysaccharide (LPS) stimulated the CSE expression and H(2)S 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 H(2)S production rate as well as NO production. l-arginine increased, whereas N(G)-nitro-l-arginine methyl ester (l-NAME) decreased LPS-induced CSE expression and H(2)S production. Dexamethasone plus l-NAME significantly decreased LPS-induced CSE expression and H(2)S production compared to l-NAME. Our results suggest that macrophages are one of the H(2)S producing sources. H(2)S might exert anti-inflammatory effects by inhibiting NO production. Dexamethasone may directly inhibit CSE expression and H(2)S production, besides the NO-dependent way. Inhibition of H(2)S and NO production may be a mechanism by which glucocorticoids coordinate the balance between pro- and anti-inflammatory mediators during inflammation.
Zhu
Xiao-Yan
XY
Department of Physiology, Second Military Medical University, 800 Xiangyin Road, 200433 Shanghai, People's Republic of China.
Liu
Shu-Juan
SJ
Liu
Yu-Jian
YJ
Wang
Shan
S
Ni
Xin
X
D000818:Animals; D002478:Cells, Cultured; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D003545:Cysteine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D003907:Dexamethasone; D003542:Cystathionine gamma-Lyase; D003545:Cysteine; D006862:Hydrogen Sulfide