Peroxisome proliferator-activated receptor-γ activation induces 11β-hydroxysteroid dehydrogenase type 1 activity in human alternative macrophages.

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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Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2012, 32 (3), pp.677-85. 〈10.1161/ATVBAHA.111.241364〉
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Giulia Chinetti-Gbaguidi, Mohamed Amine Bouhlel, Corinne Copin, Christian Duhem, Bruno Derudas, et al.. Peroxisome proliferator-activated receptor-γ activation induces 11β-hydroxysteroid dehydrogenase type 1 activity in human alternative macrophages.. Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2012, 32 (3), pp.677-85. 〈10.1161/ATVBAHA.111.241364〉. 〈inserm-00656065〉

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