KMID : 1094020140310060469
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Journal of Veterinary Clinics 2014 Volume.31 No. 6 p.469 ~ p.476
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Trans-10, cis-12 Conjugated Linoleic Acid Modulates Tumor Necrosis Factor-¥á Production and Nuclear Factor-¥êB Activation in RAW 264.7 Macrophages Through Formation of Reactive Oxygen Species
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Park So-Young
Kang Ji-Houn Yang Mhan-Pyo Kang Byeong-Teck
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Abstract
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The aims of this study were to explore the effects of conjugated linoleic acid (CLA) on reactive oxygenspecies (ROS) production in lipopolysaccharide (LPS)-naive and LPS-stimulated RAW 264.7 macrophages and toexamine whether these effects affect the regulation of tumor necrosis factor-alpha (TNF-¥á) production, and nuclearfactor-kappa B (NF-¥êB) and peroxisome proliferator-activated receptor gamma (PPAR¥ã) activation. Trans-10, cis-12(t10c12)-CLA increased the production of ROS, as well as TNF-¥á in LPS-naive RAW 264.7 cells. The CLA-inducedTNF-¥á production was suppressed by treatment of diphenyleneiodonium chloride (DPI), a NADPH oxidase inhibitor. In addition, CLA enhanced the activities of NF-¥êB and PPAR¥ã in LPS-naive RAW 264.7 cells, and this effect wasabolished with DPI treatment. LPS treatment increased ROS production, whereas CLA reduced LPS-induced ROSproduction. LPS increased both TNF-¥á production and NF-¥êB activity, whereas t10c12-CLA reduced TNF-¥á productionand NF-¥êB activity in LPS-stimulated RAW 264.7 cells. DPI treatment suppressed LPS-induced ROS production andNF-¥êB activity. Moreover, DPI enhanced the inhibitory effects of t10c12-CLA on TNF-¥á production and NF-¥êBactivation in LPS-stimulated RAW 264.7 cells. However, neither t10c12-CLA nor DPI affected PPAR¥ã activity in LPSstimulatedRAW 264.7 cells. Taken together, these data indicate that t10c12-CLA induces TNF-¥á production byincreasing ROS production in LPS-naive RAW 264.7 cells, which is mediated by the enhancement of NF-¥êB activityvia PPAR¥ã activation. By contrast, t10c12-CLA suppresses TNF-¥á production by inhibiting ROS production and NF-¥êB activation via a PPAR¥ã-independent pathway in LPS-stimulated RAW 264.7 cells. These results suggest that t10c12-CLA can modulate TNF-¥á production and NF-¥êB activation through formation of ROS in RAW 264.7 macrophages.
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KEYWORD
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conjugated linoleic acid, lipopolysaccharide, tumor necrosis factor-alpha, nuclear factor-kappa B, reactive oxygen species, peroxisome proliferator-activated receptor gamma, RAW 264.7 macrophages
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