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

Innate Immunity

M RachelRichards¹ 

关键词: TRIF;    MyD88;    TLR3;    murine models;    inflammation;    atherosclerosis;   

DOI  :  10.1177/1753425912447130

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

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 TRIFLps2 lack-of-function mutation was atheroprotective in hyperlipidemic low density lipoprotein (LDL) receptor knockout (LDLr−/−) mice. LDLr−/− mice were crossed with either TRIFLps2 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 TRIFLps2 were significantly protected from atherosclerosis. TRIFLps2 led to a reduction in cytokines secreted from peritoneal macrophages (Mϕ) in response to hyperlipidemia. Moreover, heart sinus valves from hyperlipidemic LDLr−/−TRIFLps2 mice had significantly fewer lesional Mϕ. However, LDLr−/− mice deficient in TLR3 showed some enhancement of disease. Collectively, these data ...

【 授权许可】

CC BY