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

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 wi...