Myeloid Differentiation Primary Response Protein 88 Couples Reverse Cholesterol Transport to Inflammation

Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Cell metabolism (Impact Factor: 17.57). 06/2010; 11(6):493-502. DOI: 10.1016/j.cmet.2010.04.006
Source: PubMed


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.

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    • "ages , TLR2 and TLR4 suppress stimulation of LXRs through both myeloid differentiation primary response gene ( MyD ) 88 - dependent and independent pathways while apolipoprotein A1 , an essential protein component of high density lipoprotein ( HDL ) particles and TLR2 , TLR4 , and CD14 agonist , utilizes MyD88 - dependent mechanism to induce RCT ( Smoak et al . , 2010 ) . In summary , LXRs play a remarkable role on crossroads of metabolic , cell cycle , and immune signaling ."
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