INSERM UMR-911 CRO2, Aix-Marseille Université, Faculté de Médecine-Timone, 27 Bld Jean Moulin, 13385 Marseille Cedex 05, France.
Arch Biochem Biophys. 2010 Mar 1;495(1):56-61. doi: 10.1016/j.abb.2009.12.019. Epub 2009 Dec 24.
Lipopolysaccharides (LPS) are major components of the cell wall of Gram negative bacteria implicated in the pathogenesis of bacterial infection. Resveratrol is a polyphenolic phytoalexin exhibiting antioxidant and anti-inflammatory properties. We investigated the protective effects of this natural compound on LPS-induced proinflammatory effect using non-myeloid AR42J pancreatic cells. We found that LPS dose-dependently increased extracellular malondialdehyde (MDA) and nitric oxide without affecting their intracellular level whereas resveratrol abolished all these deleterious effects. LPS increased CD14 expression; IRAK1 and a phosphorylated form of p38 MAPK protein. Resveratrol counteracted LPS effect by decreasing CD14 and IRAK1 expression but unexpectedly increased the p38 MAPK protein phosphorylation. Altogether, our data highlighted the functionality of the TLR4-Myd88 signaling pathway in LPS pro-oxidant effect using non-myeloid cells. They further suggested that resveratrol exerted antioxidant properties either by a Myd88-dependent way not involving IRAK1 or by a TRIF dependent pathway.
脂多糖（LPS）是革兰氏阴性菌细胞壁的主要成分，与细菌感染的发病机制有关。白藜芦醇是一种多酚类植物抗毒素，具有抗氧化和抗炎特性。我们使用非髓样 AR42J 胰腺细胞研究了这种天然化合物对 LPS 诱导的促炎作用的保护作用。我们发现 LPS 剂量依赖性地增加细胞外丙二醛（MDA）和一氧化氮，而不影响其细胞内水平，而白藜芦醇消除了所有这些有害作用。LPS 增加了 CD14 的表达；IRAK1 和磷酸化形式的 p38 MAPK 蛋白。白藜芦醇通过降低 CD14 和 IRAK1 的表达来拮抗 LPS 的作用，但出乎意料的是增加了 p38 MAPK 蛋白的磷酸化。总之，我们的数据强调了 TLR4-Myd88 信号通路在非髓样细胞 LPS 促氧化作用中的功能。它们进一步表明，白藜芦醇通过依赖 Myd88 的方式发挥抗氧化特性，不涉及 IRAK1 或通过 TRIF 依赖的途径。
