Peroxisome Proliferator-activated Receptor-γ Activation Induces 11β-hydroxysteroid Dehydrogenase Type 1 Activity in Human Alternative Macrophages

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2011 Dec 31

PMID 22207732

Citations 16

Authors

Giulia Chinetti-Gbaguidi

Mohamed Amine Bouhlel

Corinne Copin

Christian Duhem

Bruno Derudas

Bernadette Neve

Benoit Noel

Jerome Eeckhoute

Philippe Lefebvre

Jonathan R Seckl

Bart Staels

Affiliations

Soon will be listed here.

Abstract

Objective: 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the intracellular reduction of inactive cortisone to active cortisol, the natural ligand activating the glucocorticoid receptor (GR). Peroxisome proliferator- activated receptor-γ (PPARγ) is a nuclear receptor controlling inflammation, lipid metabolism, and the macrophage polarization state. In this study, we investigated the impact of macrophage polarization on the expression and activity of 11β-HSD1 and the role of PPARγ therein.

Methods And Results: 11β-HSD1 gene expression is higher in proinflammatory M1 and anti-inflammatory M2 macrophages than in resting macrophages, whereas its activity is highest in M2 macrophages. Interestingly, PPARγ activation induces 11β-HSD1 enzyme activity in M2 macrophages but not in resting macrophages or M1 macrophages. Consequently, human M2 macrophages displayed enhanced responsiveness to the 11β-HSD1 substrate cortisone, an effect amplified by PPARγ induction of 11β-HSD1 activity, as illustrated by an increased expression of GR target genes.

Conclusion: Our data identify a positive cross-talk between PPARγ and GR in human M2 macrophages via the induction of 11β-HSD1 expression and activity.

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