Sterol regulation of scavenger receptor class B type I in macrophages

Liqing Yu, Guoqing Cao, Joyce Repa, Herbert Stangl

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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 LXRα and LXRβ. 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.

Original languageEnglish (US)
Pages (from-to)889-899
Number of pages11
JournalJournal of lipid research
Volume45
Issue number5
DOIs
StatePublished - May 1 2004

Keywords

  • Cholesterol
  • Mouse scavenger receptor class B type I promoter
  • Regulation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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