Identification of a gamma-interferon-responsive element in the promoter of the human macrophage scavenger receptor A gene.
In the present study, we demonstrate gamma-interferon (gamma-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 (gamma-interferon activation site) in the SR-A promoter demonstrates gamma-IFN-inducible DNA binding activity and is most likely responsible for the gamma-IFN-dependent expression of an SR-A promoter-luciferase fusion construct. In contrast, gamma-IFN inhibits SR-A expression in mature macrophages as well as after prolonged gamma-IFN incubation of THP-1 monocytes. Taken together, these results demonstrate opposite effects of gamma-IFN on SR-A expression and activity during the early versus late stages of monocyte maturation. gamma-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.
Grewal
T
T
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.
Priceputu
E
E
Davignon
J
J
Bernier
L
L
D000328:Adult; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005796:Genes; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D051116:Receptors, Scavenger; D020218:Response Elements; D050794:STAT1 Transcription Factor; D051117:Scavenger Receptors, Class A; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D051117:Scavenger Receptors, Class A; D015534:Trans-Activators; D007371:Interferon-gamma