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Originally published In Press as doi:10.1194/jlr.M300461-JLR200 on February 16, 2004

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

Sterol regulation of scavenger receptor class B type I in macrophages

Liqing Yu1,*, Guoqing Cao*, Joyce Repa{dagger} and Herbert Stangl2,1,*

* Department of Molecular Genetics and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390
{dagger} 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{alpha} 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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