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Papers In Press, published online ahead of print February 16, 2004
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Medical Chemistry, University of Vienna, Vienna 1090
Corresponding Author: herbert.stangl{at}univie.ac.at
The 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 down-regulation 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 expression of a luciferase reporter placed downstream of a 2,556 bp of 5’-flanking sequence from mouse SR-BI gene. Reduction in SR-BI expression was also seen in sterol loaded peritoneal macrophages from mice expressing no LXR alpha and LXR beta. We conclude that SR-BI levels in macrophages are responsive to changes in the intracellular sterol content and that these sterol-associated changes are not mediated by LXR and unlikely by an SREBP pathway.
Revised on February 3, 2004
Accepted on February 6, 2004
Sterol regulation of scavenger receptor class B type I in macrophages
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