Peroxisome proliferator-activated receptor-γ activation induces 11β-hydroxysteroid dehydrogenase type 1 activity in human alternative macrophages. - Archive ouverte HAL Access content directly
Journal Articles Arteriosclerosis, Thrombosis, and Vascular Biology Year : 2012

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

(1) , (1) , (1) , (1) , (1) , (2) , (1) , (1) , (1) , (3) , (1)
1
2
3

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.
Fichier principal
Vignette du fichier
inserm-00656065_edited.pdf (334.34 Ko) Télécharger le fichier
Vignette du fichier
Bouhlel_dec2011.pdf (382.56 Ko) Télécharger le fichier
Vignette du fichier
supplement_tables_legends_and_figures_R1.pdf (26.63 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Loading...

Dates and versions

inserm-00656065 , version 1 (29-06-2012)

Identifiers

Cite

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, 2012, 32 (3), pp.677-85. ⟨10.1161/ATVBAHA.111.241364⟩. ⟨inserm-00656065⟩
200 View
428 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More