BioEssays : news and reviews in molecular, cellular and developmental biology
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Interleukin-1 receptor-associated kinase-1 (IRAK1) is linked to the pathogenesis of atherosclerosis; however, its role in macrophage foam cell formation is not known. Therefore, the present study investigated the role of IRAK1 in lipid uptake, biosynthesis, and efflux in THP-1 derived macrophages and human monocyte-derived macrophages (HMDMs). Ox-LDL (40 μg/mL, 15 minutes-48 hours) treatment induced time-dependent increase in IRAK1, IRAK4, and Stat1 activation in THP-1 derived macrophages. ⋯ In IRAK1/4 INH pre-treated THP-1 derived macrophages Ox-LDL-induced Stat1 phosphorylation and its binding to CD36 promoter was significantly attenuated while LXRα expression and its binding to the ABCA1/ABCG1 locus, NFATc2 activation and its binding to ABCA1 locus was enhanced. The present study thus demonstrates that IRAK regulates lipid accumulation by modulating CD36-mediated uptake and ABCA1-, ABCG1-dependent cholesterol efflux. Therefore, IRAK1 can be a potential target for preventing macrophage foam cell formation.