Regulation Of Cystathionine-gamma-lyase By Endotoxin And Glucocorticoids In RAW264.7 Cells And The Mechanisms

Hydrogen sulfide (H2S) can be endogenously produced in mammalian tissues from cysteine by cystathionine-γ-lyase (CSE). Endogenous H2S exerts many important physiological functions,and might play an important role in the pathogenesis of inflammatory deseases. It was demonstrated that both H2S formation in various tissues and CSE expression and activity were markedly increased in septic or endotoxic shock,but the mechanisms involved in the regulation of CSE expression still remains unclear. In the first part of this study, we first confirmed that lipopolysaccharides (LPS) significantly induced the expression of CSE mRNA and protein in cultured murine macrophage cell line RAW264.7, then the signal transduction pathways involved in LPS induced CSE expression were investigated. The results indicated that NF-κB, PKC and PI3K signaling pathways might be involved in the regulation of LPS induced CSE expression. Glucocorticoids (GCs) are widely used for the treatment of inflammatory diseases including endotoxin and septic shock. The inhitory effects of GCs on the production of another pro-inflammatory gaseous mediator, nitric oxide (NO), and on the expression of NO synthase have long been recognized. However, whether GCs have the similar effects on CSE expression remains unclear. Therefore in the second part of this study, we investigated whether dexamethasone(DEX)could inhibit the LPS induced CSE expression in murine RAW264.7 macrophages. Our results showed that DEX significantly inhibited LPS induced CSE expression (mRNA and protein) and CSE promoter activity.