中文摘要：

炎症因子的表达调控是炎症反应的关键步骤，与自身免疫疾病以及癌症等密切相关．一氧化氮（nitricoxide，NO）在炎症因子表达调控中具有重要作用，但已有的研究多关注于NO合成对炎症因子的调控作用，而对NO代谢的作用知之甚少．亚硝基化谷胱甘肽还原酶（s-nitrosoglutathione reductase，GSNOR）是体内NO信号通路代谢调控的关键蛋白．本研究发现脂多糖（1ipopolysaccharide，LPS）在RAW264．7细胞中上调诱导型一氧化氮合酶（induciblenitricoxidesynthase，iNOSl的同时下调GSNOR的转录和蛋白质表达，该下调作用依赖MEKl／2、p38和P13K信号通路．抑制GSNOR可促进LPS诱导的炎症因子几-lB、IL-6和TNF．仪表达，而过表达GSNOR作用相反．抗炎症药物曲古抑菌素A（trichostatinA，TSA）~够挽回LPS对GSNOR的下调作用，并且GSNOR抑制剂削弱了TSA对炎症因子IL．6和TNF．仪转录的抑制效应．这些结果表明：GSNOR是一个新的重要炎症调控分子，它可能成为调控NO介导的炎症相关信号通路的新的潜在靶点，上调GSNOR可能是抑制炎症的新思路．本研究揭示了巨噬细胞通过上调iNOS和下调GSNOR共同增强免疫炎症反应的新机制，拓展了对NO代谢在炎症反应中作用机制的认识．

英文摘要：

Regulation of inflammatory cytokines is a critical stage in inflammation, an important factor in autoimmune disease and cancer. Nitric oxide （NO） is known to be an important regulator of inflammatory cytokines, however, most existing studies focus on the role of NO synthesis in the regulation of inflammatory cytokines, and little is known about the role of NO metabolism. Since S-nitrosoglutathione reductase （GSNOR） is a key protein in the control of NO metabolism, investigating its role in inflammation will be important for understanding the role of NO metabolism. Here we found that GSNOR transcription and protein expression is downregulated by lipopolysaccharide （LPS） in RAW264.7 ceils, an inflammatory cell model. Inhibitors of MEK1/2, p38 and PI3K significantly attenuate the decrease in GSNOR transcription. Furthermore, inhibition of the enzyme activity of GSNOR promoted expression of LPS-induced inflammatory cytokines IL- 1 β, IL-6 and TNF-α, whereas overexpression of GSNOR had the opposite effect. The anti-inflammatory drug trichostatin A （TSA） rescued the downregulation of GSNOR expression by LPS. Furthermore, inhibition of GSNOR impaired the anti-inflammatory effect of TSA by increasing the expression of IL-6 and TNF-α. In conclusion, our work reveals a new mechanism used by macrophage cells to enhance the inflammatory response by simultaneously upregulating inducible nitric oxide synthase （iNOS） and downregulating GSNOR, thus expanding our understanding of NO metabolism in inflammatory responses. This study shows that GSNOR is a novel regulator of inflammation and may be a potential target for the regulation of NO-mediated inflammation.