G protein pathway suppressor 2 (GPS2) links inflammation and cholesterol efflux by controlling lipopolysaccharide-induced ATP-binding cassette transporter A1 expression in macrophages

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Zhiqiang HuangEckardt Treuter

Abstract

Macrophages play important roles in linking alterations of cholesterol metabolism and inflammation to the development of atherosclerosis. Previous studies have identified several positive and negative crosstalk mechanisms that connect cholesterol efflux and inflammation at the transcriptional level. Of particular relevance is that the expression of ATP-binding cassette transporter A1 ( Abca1), a main regulator of cholesterol efflux, can be induced by oxysterol receptor LXR agonists but also by bacterial endotoxins, such as LPS, that activate TLR4 signaling. However, the extent to which these pathways influence each other has remained incompletely understood. We investigated the possible role of the transcriptional coregulator G protein pathway suppressor 2 (GPS2) in LPS-induced Abca1 expression and cholesterol efflux in mouse and human macrophages. To activate Abca1, GPS2 cooperates with the LPS-inducible NF-κB subunit p65, but not with LXRs nor with corepressor complex subunits that otherwise cooperate with GPS2 to repress proinflammatory gene expression. Overall, our work identifies a regulatory chromatin component of crosstalk mechanisms between cholesterol efflux and inflammation that specifically affects ABCA1. Because GPS...Continue Reading

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Citations

May 13, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhanfang Kang, Rongrong Fan
Jun 20, 2020·Blood·Lily Jun-Shen Huang, James J Bieker
Jul 12, 2019·Frontiers in Endocrinology·Ning LiangEckardt Treuter
Aug 11, 2020·Nutrition & Metabolism·Zixiang YeTao Wu

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