TNFalpha induces ABCA1 through NF-kappaB in macrophages and in phagocytes ingesting apoptotic cells.

ABSTRACT: Recent evidence suggests that tumor necrosis factor alpha (TNFalpha) signaling in vascular cells can have antiatherogenic consequences, but the mechanisms are poorly understood. TNFalpha is released by free cholesterol-loaded apoptotic macrophages, and the clearance of these cells by phagocytic macrophages may help to limit plaque development. Macrophage cholesterol uptake induces ATP-binding cassette (ABC) transporter ABCA1 promoting cholesterol efflux to apolipoprotein A-I and reducing atherosclerosis. We show that TNFalpha induces ABCA1 mRNA and protein in control and cholesterol-loaded macrophages and enhances cholesterol efflux to apolipoprotein A-I. The induction of ABCA1 by TNFalpha is reduced by 65% in IkappaB kinase beta-deficient macrophages and by 30% in p38alpha-deficient macro

SUBMITTER: Gerbod-Giannone MC 

PROVIDER: S-EPMC1413897 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature