Expression and regulation of sterol 27-hydroxylase (CYP27A1) in human macrophages: a role for RXR and PPARgamma ligands

  • Biochem J. 2005 Feb 1;385(Pt 3):823-30. doi: 10.1042/BJ20041776.
Carmel M Quinn  1 ,  Wendy Jessup ,  Jenny Wong ,  Leonard Kritharides ,  Andrew J Brown
Affiliations
  • 1. Centre for Vascular Research, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
PMID: 15533057 DOI: 10.1042/BJ20041776
Abstract

CYP27A1 (sterol 27-hydroxylase) catalyses an important sterol elimination pathway in the human macrophage, and consequently may protect against atherosclerosis. We studied the expression and regulation of CYP27A1 in a human macrophage-like cell-line, THP-1, and primary HMDMs (human monocyte-derived macrophages). In both macrophage cell types, we found that CYP27A1 expression is independent of cellular Cholesterol levels and of LXR (liver X receptor)-dependent control of transcription. However, the RXR (retinoid X receptor) ligand, 9-cis-retinoic acid, upregulates CYP27A1 expression. Of the RXR heterodimeric partners tested, PPAR (peroxisome-proliferator-activated receptor) gamma ligands significantly increased CYP27A1 mRNA levels. Its reversal by a PPARgamma antagonist demonstrated the specificity of this effect. Interestingly, HMDMs express markedly higher levels of CYP27A1 than THP-1 macrophages, and this difference was reflected in both protein levels and enzyme activities between the two cell types. In conclusion, stimulation of CYP27A1 by PPARgamma may represent a key previously unrecognized mechanism by which PPARgamma protects against atherosclerosis.

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