Oxidized phospholipid-induced inflammation is mediated by Toll-like receptor 2.

Published

Journal Article

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-glycerophosphorylcholine (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 cofactors. Finally, TLR2(-/-) mice were protected against carbon tetrachloride-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.

Full Text

Cited Authors

  • Kadl, A; Sharma, PR; Chen, W; Agrawal, R; Meher, AK; Rudraiah, S; Grubbs, N; Sharma, R; Leitinger, N

Published Date

  • November 2011

Published In

Volume / Issue

  • 51 / 10

Start / End Page

  • 1903 - 1909

PubMed ID

  • 21925592

Pubmed Central ID

  • 21925592

Electronic International Standard Serial Number (EISSN)

  • 1873-4596

International Standard Serial Number (ISSN)

  • 0891-5849

Digital Object Identifier (DOI)

  • 10.1016/j.freeradbiomed.2011.08.026

Language

  • eng