Myeloid differentiation primary response protein 88 couples reverse cholesterol transport to inflammation.
Cell Metab, 2010/6/09;11(6):493-502.
Smoak KA[1], Aloor JJ, Madenspacher J, Merrick BA, Collins JB, Zhu X, Cavigiolio G, Oda MN, Parks JS, Fessler MB
Affiliations
PMID: 20519121DOI: 10.1016/j.cmet.2010.04.006
Impact factor: 31.373
Abstract
Crosstalk exists in mammalian cells between cholesterol trafficking and innate immune signaling. Apolipoprotein A-I (apoA-I), a serum apolipoprotein that induces antiatherogenic efflux of macrophage cholesterol, is widely described as anti-inflammatory because it neutralizes bacterial lipopolysaccharide. Conversely, lipopolysaccharide-induced inflammation is proatherogenic. However, whether innate immunity plays an endogenous, physiological role in host cholesterol homeostasis in the absence of infection is undetermined. We report that apoA-I signals in the macrophage through Toll-like receptor (TLR)2, TLR4, and CD14, utilizing myeloid differentiation primary response protein 88 (MyD88)-dependent and -independent pathways, to activate nuclear factor-kappaB and induce cytokines. MyD88 plays a critical role in reverse cholesterol transport in vitro and in vivo, in part through promoting ATP-binding cassette A1 transporter upregulation. Taken together, this work identifies apoA-I as an endogenous stimulus of innate immunity that couples cholesterol trafficking to inflammation through MyD88 and identifies innate immunity as a physiologic signal in cholesterol homeostasis.
MeSH terms
ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; Animals; Apolipoprotein A-I; Biological Transport; Cell Differentiation; Cholesterol; Cytokines; Immunity, Innate; Inflammation; Lipopolysaccharide Receptors; Lipopolysaccharides; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid Differentiation Factor 88; NF-kappa B; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4
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