| First Author | Smoak KA | Year | 2010 |
| Journal | Cell Metab | Volume | 11 |
| Issue | 6 | Pages | 493-502 |
| PubMed ID | 20519121 | Mgi Jnum | J:160911 |
| Mgi Id | MGI:4456301 | Doi | 10.1016/j.cmet.2010.04.006 |
| Citation | Smoak KA, et al. (2010) Myeloid differentiation primary response protein 88 couples reverse cholesterol transport to inflammation. Cell Metab 11(6):493-502 |
| abstractText | 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. |
