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首页> 外文期刊>Applied Microbiology and Biotechnology >Inhibition of hydrogen sulfide production by gene silencing attenuates inflammatory activity of LPS-activated RAW264.7 cells
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Inhibition of hydrogen sulfide production by gene silencing attenuates inflammatory activity of LPS-activated RAW264.7 cells

机译:通过基因沉默抑制硫化氢产生减弱了LPS激活的RAW264.7细胞的炎症活性

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摘要

Hydrogen sulfide is an inflammatory mediator and is produced by the activity of the enzyme cystathionine γ-lyase (CSE) in macrophages. Previously, pharmacological inhibition of CSE has been reported to have conflicting results, and this may be due to the lack of specificity of the pharmacological agents. Therefore, this study used a very specific approach of small interfering RNA (siRNA) to inhibit the production of the CSE in an in vitro setting.We found that the activation of macrophages by lipopolysaccharide (LPS) resulted in higher levels of CSE mRNA and protein as well as the increased production of proinflammatory cytokines and nitric oxide (NO).We successfully used siRNA to specifically reduce the levels of CSE mRNA and protein in activated macrophages. Furthermore, the levels of proinflammatory cytokines in LPS-activated macrophages were significantly lower in siRNA-transfected cells compared to those in untransfected controls. However, the production levels of NO by the transfected cells were higher, suggesting that CSE activity has an inhibitory effect on NO production. These findings suggest that the CSE enzyme has a crucial role in the activation of macrophages, and its activity has an inhibitory effect on NO production by these cells.
机译:硫化氢是一种炎症介质,是由巨噬细胞中胱硫醚γ-裂解酶(CSE)的活性产生的。以前,据报道对CSE的药理抑制作用有矛盾的结果,这可能是由于药理剂缺乏特异性所致。因此,本研究使用非常特殊的方法在体外环境中抑制小干扰RNA(siRNA)的产生。我们发现脂多糖(LPS)激活巨噬细胞会导致CSE mRNA和蛋白水平升高以及增加促炎细胞因子和一氧化氮(NO)的产生。我们成功地使用siRNA特异性降低了活化巨噬细胞中CSE mRNA和蛋白质的水平。此外,与未转染的对照相比,在siRNA转染的细胞中,LPS活化的巨噬细胞中促炎细胞因子的水平显着降低。然而,转染细胞产生的NO的水平较高,表明CSE活性对NO的产生具有抑制作用。这些发现表明,CSE酶在巨噬细胞的活化中起关键作用,并且其活性对这些细胞的NO产生具有抑制作用。

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