title: Glucocorticoids suppress cystathionine gamma-lyase expression and H2S production in lipopolysaccharide-treated macrophages.
abstract: 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.
authors.affiliation: Department of Physiology, Second Military Medical University, 800 Xiangyin Road, 200433 Shanghai, People's Republic of China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhu
authors.forename: Shu-Juan
authors.initials: SJ
authors.lastname: Liu
authors.forename: Yu-Jian
authors.initials: YJ
authors.lastname: Liu
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
mesh_terms: 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
chemical_list: D005938:Glucocorticoids; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D003907:Dexamethasone; D003542:Cystathionine gamma-Lyase; D003545:Cysteine; D006862:Hydrogen Sulfide