کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2536291 | 1559149 | 2007 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Effect of PPARα activation of macrophages on the secretion of inflammatory cytokines in cultured adipocytes Effect of PPARα activation of macrophages on the secretion of inflammatory cytokines in cultured adipocytes](/preview/png/2536291.png)
The relationship between adipocytes and infiltrated macrophages in fat tissue is important for the pathogenesis of insulin resistance through the activation of cytokines. Peroxisome proliferator-activated receptors (PPARs) play a role in the regulation of cytokine secretion in these cells. We studied the effect of the PPARα activation of macrophages on the modulation of the tumor necrosis factor α (TNFα) expression in adipocytes using a cell culture system. A conditioned medium of lipopolysaccharide (LPS)-stimulated RAW264.7 cells, a macrophage cell line, induced the level of TNFα mRNA in 3T3-L1 adipocytes. This effect was inhibited by the addition of neutralizing antibody against interleukin 6 (IL-6) in the conditioned medium or the preincubation of RAW264.7 cells with a specific PPARα agonist, K-111 (2,2-dichloro-12-(4-chlorophenyl)dodecanoic acid). K-111 reduced both the IL-6 production and mRNA expression in RAW264.7 cells, and its effect was stronger than that of rosiglitazone, a PPARγ agonist. The activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) pathway and nuclear factor kappa B (NF-κB) subunits of p65 was significantly inhibited by K-111. The blocking of IL-6 production through the SAPK/JNK pathway or by transfection with siRNA specific for IL-6 abolished the inhibitory effect of K-111 on the TNFα expression in the 3T3-L1 adipocytes. As a result, the IL-6 produced by RAW264.7 cells is an inducer of TNFα expression in 3T3-L1 adipocytes, and the IL-6 secretion is inhibited by the activation of PPARα. The PPARα activators may suppress the pathogenetical secretion of TNFα in the adipocytes through the functional modulation of the infiltrated macrophages.
Journal: European Journal of Pharmacology - Volume 561, Issues 1–3, 30 April 2007, Pages 206–213