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首页> 外文期刊>Cytokine >Nitric oxide affects IL-6 expression in human peripheral blood mononuclear cells involving cGMP-dependent modulation of NF-kappaB activity.
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Nitric oxide affects IL-6 expression in human peripheral blood mononuclear cells involving cGMP-dependent modulation of NF-kappaB activity.

机译:一氧化氮影响人外周血单核细胞中IL-6的表达,涉及NF-κB活性的cGMP依赖性调节。

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摘要

Interleukin 6 (IL-6) and nitric oxide (NO) are important mediators of the inflammatory response. We report that in human peripheral blood mononuclear cells (PBMCs), NO exerts a biphasic effect on the expression of IL-6. Using sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO) as NO-donating compounds, we observed that both mRNA and protein levels of IL-6 increased at lower (100muM) concentrations of NO donors. Changes in the expression of IL-6 correlated with changes in the activity of NF-kappaB, which increased at lower and decreased at higher concentrations of both NO donors as shown by the electrophoretic mobility shift assay (EMSA). The effects of NO on NF-kappaB activity were cGMP-dependent because they were reversed in the presence of ODQ, the inhibitor of soluble guanylyl cyclase (sGC), and KT5823, the inhibitor of cGMP-dependent protein kinase (PKG). Moreover, the membrane permeable analog of cGMP (8-Br-cGMP) mimicked the effect of the NO donors. These observations show that NO, depending on its concentration, may act in human PBMCs as a stimulator of IL-6 expression involving the sGC/cGMP/PKG pathway.
机译:白介素6(IL-6)和一氧化氮(NO)是炎症反应的重要介质。我们报告在人类外周血单核细胞(PBMCs),NO对IL-6的表达发挥双相作用。使用硝普钠(SNP)和S-亚硝基谷胱甘肽(GSNO)作为提供NO的化合物,我们观察到IL-6的mRNA和蛋白质水平在较低浓度(100μM)时下降。没有捐助者。 IL-6表达的变化与NF-κB活性的变化相关,如电泳迁移率变动分析(EMSA)所示,NF-κB的活性在两种NO供体的浓度都较低时升高,而在较高浓度时降低。 NO对NF-κB活性的影响是cGMP依赖性的,因为它们在ODQ(可溶性鸟苷酸环化酶(sGC)的抑制剂)和KT5823(cGMP依赖性蛋白激酶(PKG)的抑制剂)的存在下被逆转。此外,cGMP(8-Br-cGMP)的膜渗透性类似物模仿了NO供体的作用。这些观察结果表明,取决于其浓度,NO可能在人PBMC中作为刺激sGC / cGMP / PKG途径的IL-6表达的作用。

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