Glucocorticoids suppress cystathionine gamma-lyase expression and H2S production in lipopolysaccharide-treated macrophages
Glucocorticoids suppress cystathionine gamma-lyase expression and H2S production in lipopolysaccharide-treated macrophages
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DOI：
10.1007/s00018-009-0250-9
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发表时间：
2010-01
影响因子：
8
通讯作者：
Xiaoyan Zhu;Shujuan Liu;Yu-Jian Liu;Shan Wang;X. Ni
中科院分区：
文献类型：
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作者：
Xiaoyan Zhu;Shujuan Liu;Yu-Jian Liu;Shan Wang;X. Ni
硫化氢（H2S）在炎症中起着重要作用。我们发现，巨噬细胞表达H2S形成酶胱硫醚γ裂解酶（CSE）并产生H2S。脂多糖（LPS）刺激CSE表达和H2S产生速率，L-半胱氨酸抑制LPS诱导的一氧化氮（NO）产生。CSE抑制剂可阻断半胱氨酸的抑制作用。CSE敲低增加，而CSE过表达减少LPS诱导的NO产生。地塞米松抑制LPS诱导的CSE表达和H2S产生速率以及NO产生，L-精氨酸增加，而NG-硝基-L-精氨酸甲酯（l-NAME）减少LPS诱导的CSE表达和H2S产生。地塞米松加l-NAME与tol-NAME相比显著降低LPS诱导的CSE表达和H2S产生。我们的研究结果表明，巨噬细胞是H2S的产生源之一。H2S可能通过抑制NO的产生而发挥抗炎作用。地塞米松除通过NO依赖的途径抑制CSE表达外，还可直接抑制H2S的产生。抑制H2S和NO的产生可能是糖皮质激素在炎症过程中协调促炎和抗炎介质之间平衡的机制。
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 ofl-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 plusl-NAME significantly decreased LPS-induced CSE expression and H2S production compared tol-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.