Regulation of sterol 27-hydroxylase in human monocyte-derived macrophages: up-regulation by transforming growth factor β1

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids 2005-02, Vol.1687 (1), p.44-51
• Main Authors: Hansson, Magnus, Wikvall, Kjell, Babiker, Amir
• Format: Article
• Language: English
• Subjects: 27-Hydroxycholesterol; 3β-Hydroxy-5-cholestenoic acid; Cholesterol; CYP27A1
• ISSN: 1388-1981; 1879-2618
• DOI: 10.1016/j.bbalip.2004.11.002

Regulatory mechanisms for human CYP27A1 enzyme have not yet been fully investigated. Our approach was to add different hormones and cytokines to cultured human monocyte-derived macrophages, and assess the effects on the CYP27A1 by measuring the production of 27-hydroxylated cholesterol in the media. Of the different hormones and cytokines tested, only transforming growth factor β1 (TGF-β1) had a clear effect on CYP27A1. Further experiments showed a significant increase in 27-hydroxylated cholesterol products (27-hydroxycholesterol and 3β-hydroxy-5-cholestenoic acid). A concomitant increase in CYP27A1 mRNA levels was also seen and this positive effect was confirmed using a human CYP27A1 luciferase reporter gene expressed in HepG2 cells. Experiments with progressive deletion/luciferase reporter gene constructs indicated that a TGF-β1 responsive sequence might be localized in a region about 400 bp upstream of the CYP27A1 translation start. The possibility is discussed that induction of CYP27A1 by TGF-β1 may be responsible for some of the anti-atherogenic properties of this cytokine.