The LPS2 mutation in TRIF is atheroprotective in hyperlipidemic low density lipoprotein receptor knockout mice.

ABSTRACT: Signaling through MyD88, an adaptor utilized by all TLRs except TLR3, is pro-atherogenic; however, it is unknown whether signaling through TIR-domain-containing adaptor-inducing interferon-β (TRIF), an adaptor used only by TLRs 3 and 4, is relevant to atherosclerosis. We determined that the TRIF(Lps2) lack-of-function mutation was atheroprotective in hyperlipidemic low density lipoprotein (LDL) receptor knockout (LDLr(-/-)) mice. LDLr(-/-) mice were crossed with either TRIF(Lps2) or TLR3 knockout mice. After feeding an atherogenic diet for 10-15 wks, atherosclerotic lesions in the heart sinus and aorta were quantitated. LDLr(-/-) mice with TRIF(Lps2) were significantly protected from atherosclerosis. TRIF(Lps2) led to a reduction in cytokines secreted from peritoneal macrophages (M) in res

SUBMITTER: Richards MR 

PROVIDER: S-EPMC3434265 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature