| First Author | Tang C | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 47 | Pages | 32336-43 |
| PubMed ID | 19783654 | Mgi Jnum | J:156325 |
| Mgi Id | MGI:4420341 | Doi | 10.1074/jbc.M109.047472 |
| Citation | Tang C, et al. (2009) The macrophage cholesterol exporter ABCA1 functions as an anti-inflammatory receptor. J Biol Chem 284(47):32336-43 |
| abstractText | ATP-binding cassette transporter A1 (ABCA1) is a cell membrane protein that exports excess cholesterol from cells to apolipoprotein (apo) A-I, the major protein in high density lipoproteins. Genetic studies have shown that ABCA1 protects against cardiovascular disease. The interaction of apoA-I with ABCA1 promotes cholesterol removal and activates signaling molecules, such as Janus kinase 2 (JAK2), that optimize the lipid export activity of ABCA1. Here we show that the ABCA1-mediated activation of JAK2 also activates STAT3, which is independent of the lipid transport function of ABCA1. ABCA1 contains two candidate STAT3 docking sites that are required for the apoA-I/ABCA1/JAK2 activation of STAT3. The interaction of apoA-I with ABCA1-expressing macrophages suppressed the ability of lysopolysaccaride to induce the inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, which was reversed by silencing STAT3 or ABCA1. Thus, the apoA-I/ABCA1 pathway in macrophages functions as an anti-inflammatory receptor through activation of JAK2/STAT3. These findings implicate ABCA1 as a direct molecular link between the cardioprotective effects of cholesterol export from arterial macrophages and suppressed inflammation. |
