title: Regulation of MSR-1 and CD36 in macrophages by LOX-1 mediated through PPAR-γ.
abstract: We observed uniform sustained Dil-ox-LDL uptake in macrophages in the presence or absence of ox-LDL receptor-1 (LOX-1). We wondered if the deficiency of LOX-1 modulates the expression of two other scavenger receptors, macrophage scavenger receptor-1 (MSR1) and CD36, on macrophages to account for the unaltered ox-LDL uptake. Macrophages were isolated from wild-type (WT) and LOX-1 knockout (KO) mice and stimulated with ox-LDL. Dil-ox-LDL uptake and expression of MSR1 and CD36 examined. Abrogation of LOX-1 did not significantly change Dil-ox-LDL uptake by macrophages. LOX-1 KO macrophages showed a significant decrease in CD36 at baseline as well as after ox-LDL stimulation and a marked almost 100% increase in the expression of MSR1, both at mRNA and protein levels (all p<0.05 vs. WT macrophages). Further, we observed a reduction in the expression of PPAR-γ in LOX-1 KO macrophages. To ascertain the role of PPAR-γ in the altered expression of MSR1 and CD36, LOX-1 KO macrophages were treated with troglitazone, a PPAR-γ agonist. Activation of PPAR-γ by troglitazone reversed the increased expression of MSR1 as well as the decreased expression of CD36 in LOX-1 KO macrophages. LOX-1 abrogation induces MSR1 and inhibits CD36 expression. The increase in MSR1 most likely accounts for sustained Dil-ox-LDL uptake despite LOX-1 abrogation. The alterations in CD36 and MSR1 occur through a decrease in PPAR-γ.
authors: University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, AR 72212, USA.
authors: Yao
authors: Y
authors: Dai
authors: Wei
authors: W
authors: Su
authors: Zufeng
authors: Z
authors: Ding
authors: Xianwei
authors: X
authors: Wang
authors: Federico
authors: F
authors: Mercanti
authors: Mingwei
authors: M
authors: Chen
authors: Sameer
authors: S
authors: Raina
authors: Jawahar L
authors: JL
authors: Mehta
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000096:biosynthesis*; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D005786:Gene Expression Regulation; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051117:Scavenger Receptors, Class A / Q000096:biosynthesis* / Q000235:genetics; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D018955:CD36 Antigens; D002839:Chromans; D008077:Lipoproteins, LDL; C495140:Msr1 protein, mouse; D016328:NF-kappa B; C495138:Olr1 protein, mouse; D047495:PPAR gamma; D051117:Scavenger Receptors, Class A; D051127:Scavenger Receptors, Class E; D045162:Thiazolidinediones; C099252:oxidized low density lipoprotein; D000077288:Troglitazone