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Journal of Lipid Research, Vol. 45, 889-899, May 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

* Department of Molecular Genetics and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390
Department of Physiology and Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390
1 To whom correspondence should be addressed. e-mail: liqing.yu{at}utsouthwestern.edu (L.U.); herbert.stangl{at}meduniwien.ac.at (H.S.)
Scavenger receptor class B type I (SR-BI) is expressed in macrophages, but its role in sterol trafficking in these cells remains controversial. We examined the effect of sterol loading on SR-BI expression in human monocytes/macrophages, mouse peritoneal macrophages, and a cultured mouse macrophage cell line (J774 cells). Sterol loading using either acetylated LDL or 25-hydroxycholesterol resulted in a time- and concentration-dependent decrease in SR-BI protein and mRNA levels. Treatment of lipid-loaded J774 cells with cyclodextrin or HDL to promote cellular sterol efflux was associated with an increase in SR-BI expression. Studies were performed to determine if the sterol-associated downregulation of SR-BI in macrophages was mediated by either sterol regulatory element binding proteins (SREBPs) or the liver X receptor (LXR). Expression of constitutively active SREBPs failed to alter the expression of a luciferase reporter placed downstream of a 2,556 bp 5' flanking sequence from the mouse SR-BI gene. Reduction in SR-BI expression was also seen in sterol-loaded peritoneal macrophages from mice expressing no LXR
and LXRß.
We conclude that SR-BI levels in macrophages are responsive to changes in intracellular sterol content and that these sterol-associated changes are not mediated by LXR and are unlikely to be mediated by an SREBP pathway.
Abbreviations: ABC, ATP binding cassette; ac-LDL, acetylated LDL; BAC, bacterial artificial chromosome; FCS, fetal calf serum; 25-HC, 25-hydroxycholesterol; LDLR, LDL receptor; LXR, liver X receptor; M-CSF, macrophage colony-stimulating factor; M-SFM, macrophage serum-free medium; NCLPPS, newborn calf lipoprotein-deficient serum; ox-LDL, oxidized LDL; PPAR, peroxisomal proliferator-activated receptor; RAP, receptor-associated protein; SCAP, SREBP cleavage-activating protein; SF-1, steroidogenic factor 1; SR-BI, scavenger receptor class B type I; SREBP, sterol regulatory element binding protein
Supplementary key words cholesterol regulation mouse scavenger receptor class B type I promoter
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