Oxidized phospholipid-induced inflammation is mediated by Toll-like receptor 2.
Oxidized phospholipid-induced inflammation is mediated by Toll-like receptor 2.
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DOI：
10.1016/j.freeradbiomed.2011.08.026
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发表时间：
2011-11-15
影响因子：
7.4
通讯作者：
Leitinger N
中科院分区：
文献类型：
--
作者：
Kadl A;Sharma PR;Chen W;Agrawal R;Meher AK;Rudraiah S;Grubbs N;Sharma R;Leitinger N
氧化性组织损伤是许多慢性炎症性疾病的标志。然而，将氧化变化与炎症反应联系起来的确切机制尚不清楚。本研究表明toll样受体2 （TLR2）通过介导氧化磷脂的作用将氧化组织损伤转化为炎症反应。在野生型小鼠中，腹腔注射氧化的1-棕榈酰-2-花生四烯基- n-3-甘油磷酸化胆碱（OxPAPC）导致炎症基因上调，但在TLR2−/−小鼠中没有。在体外，OxPAPC诱导巨噬细胞中TLR2（而不是TLR4）依赖性炎症基因表达和JNK和p38信号传导。诱导tlr2依赖性基因表达需要氧化磷脂sn-2酰基链上可还原的官能团，以及血清辅助因子。最后，TLR2 - / -小鼠被保护免受四氯化碳诱导的氧化组织损伤和炎症，这伴随着肝脏中氧化磷脂的积累。总之，我们的研究结果表明，TLR2介导细胞对氧化组织损伤的反应，并为氧化应激与急性和慢性炎症的联系提供了新的见解。
Oxidative tissue damage is a hallmark of many chronic inflammatory diseases. However, the precise mechanisms linking oxidative changes to inflammatory reactions remain unclear. Herein we show that Toll-like receptor 2 (TLR2) translates oxidative tissue damage into inflammatory responses by mediating the effects of oxidized phospholipids. Intraperitoneal injection of oxidized 1-palmitoyl-2-arachidonyl-sn-3-glycero-phosphorylcholine (OxPAPC) resulted in upregulation of inflammatory genes in wild-type, but not in TLR2−/− mice. In vitro, OxPAPC induced TLR2 (but not TLR4)-dependent inflammatory gene expression and JNK and p38 signaling in macrophages. Induction of TLR2-dependent gene expression required reducible functional groups on sn-2 acyl chains of oxidized phospholipids, as well as serum co-factors. Finally, TLR2−/− mice were protected against carbontetrachloride-induced oxidative tissue damage and inflammation, which was accompanied by accumulation of oxidized phospholipids in livers. Together, our findings demonstrate that TLR2 mediates cellular responses to oxidative tissue damage and they provide new insights into how oxidative stress is linked to acute and chronic inflammation.