The spin trap 5,5-dimethyl-1-pyrroline N-oxide inhibits lipopolysaccharide-induced inflammatory response in RAW 264.7 cells

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• 作者：Zili Zhai^a ; ^{zlzhai@yahoo.com} ; Sandra E. Gomez-Mejiba^a ; ¹ ; Hua Zhu^b ; Florea Lupu^b ; Dario C. Ramirez^a ; ¹ ; ^{ramirezlabimibiosl@ymail.com}
• 关键词：5 ; 5-dimethyl-1-pyrroline N-oxide ; Free radical ; Inflammation ; Lipopolysaccharide ; Macrophage ; NF-魏B
• 刊名：Life Sciences
• 出版年：2012
• 期刊代码：62_00243205
• 类别：imm
• 出版时间：10 March, 2012
• 卷：90
• 期：11-12
• 页码：432-439
• 文件大小：719 K

摘要

Aim

Exposure of macrophages to lipopolysaccharide (LPS) induces oxidative and inflammatory stresses, which cause cell damage. Antioxidant and anti-inflammatory properties have been attributed to the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), commonly used in free radical analysis, but these aspects of DMPO have been little explored. In this study, we sought to establish the anti-inflammatory activity of DMPO, presumably by removing free radicals which otherwise help activate inflammatory response and damage cells.

Main methods

RAW 264.7 macrophages were treated with LPS and/or DMPO for different time points, cell damage, production of inflammatory mediators, inducible nitric oxide synthase (iNOS) expression, NF-魏B p65 activation, phosphorylation of MAPKs and Akt, and intracellular reactive oxygen species (ROS) were determined.

Key findings

After cells were treated with LPS and/or DMPO for 24 h, DMPO reduced the LPS-induced inflammatory response as indicated by downregulated iNOS expression and production of inflammatory mediators. Accordingly, DMPO protected cells from LPS-induced cytotoxicity. In order to understand the mechanistic basis of these DMPO effects, the NF-魏B p65 activation and the phosphorylation of MAPKs and Akt were examined. We found, by assaying cells treated with LPS and/or DMPO for 15-60 min, that DMPO inhibited the phosphorylation of MAPKs, Akt, and I魏B伪, and reduced the NF-魏B p65 translocation. Furthermore, we demonstrated that DMPO inhibited LPS-induced ROS production.

Significance

DMPO showed the anti-inflammatory activity and attenuated LPS-induced cell damage, most likely by reducing ROS production and thus preventing the subsequent inflammatory activation and damage.