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

In the present study, we demonstrate gamma -interferon (gamma -IFN)-inducib le scavenger receptor A (SR-A) mRNA expression during the early stages of T HP-1 and blood monocyte differentiation. Predominant induction of SR-A type II mRNA parallels the increased accumulation of cholesteryl esters under t hese conditions. A potential signal transducer and activator of transcripti on (STAT1) binding site (gamma -interferon activation site) in the SR-A pro moter demonstrates gamma -IFN-inducible DNA binding activity and is most li kely responsible for the gamma -IFN-dependent expression of an SR-A promote r-luciferase fusion construct. In contrast, gamma -IFN inhibits SR-A expres sion in mature macrophages as well as after prolonged gamma -IFN incubation of THP-1 monocytes. Taken together, these results demonstrate opposite eff ects of gamma -IFN on SR-A expression and activity during the early versus late stages of monocyte maturation. gamma -IFN-induced STAT1 activation, le ading to increased SR-A expression, could therefore play an important role in the initial steps of foam cell formation and xanthomatosis.