An innate immunity signaling process suppresses macrophage ABCA1 expression through IRAK-1-mediated downregulation of retinoic acid receptor alpha and NFATc2.

ABSTRACT: ATP-binding cassette transporter A1 (ABCA1) plays a central role in promoting cholesterol efflux from macrophages, thereby reducing the risk of foam cell formation and atherosclerosis. The expression of ABCA1 is induced by members of the nuclear receptor family of transcription factors, including retinoic acid receptors (RARs). A key innate immunity signaling kinase, IRAK-1, has been associated with an increased risk of atherosclerosis in humans and mice. This prompted us to investigate the potential connection between IRAK-1 and the expression of ABCA1. Here, we demonstrate that nuclear RARalpha levels are dramatically elevated in IRAK-1(-/-) macrophages. Correspondingly, IRAK-1(-/-) macrophages exhibit increased expression of ABCA1 mRNA and protein, as well as elevated cholesterol efflux

SUBMITTER: Maitra U 

PROVIDER: S-EPMC2772564 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature