Identification of a γ-interferon responsive element in the promoter of the human macrophage scavenger receptor A gene

Abstract

In the present study, we demonstrate γ-interferon (γ-IFN)-inducible scavenger receptor A (SR-A) mRNA expression during the early stages of THP-1 and blood monocyte differentiation. Predominant induction of SR-A type II mRNA parallels the increased accumulation of cholesteryl esters under these conditions. A potential signal transducer and activator of transcription (STAT1) binding site (γ-interferon activation site) in the SR-A promoter demonstrates γ-IFN-inducible DNA binding activity and is most likely responsible for the γ-IFN-dependent expression of an SR-A promoter-luciferase fusion construct. In contrast, γ-IFN inhibits SR-A expression in mature macrophages as well as after prolonged γ-IFN incubation of THP-1 monocytes. Taken together, these results demonstrate opposite effects of γ-IFN on SR-A expression and activity during the early versus late stages of monocyte maturation. γ-IFN-induced STAT1 activation, leading to increased SR-A expression, could therefore play an important role in the initial steps of foam cell formation and xanthomatosis.