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Peroxisome Proliferator-Activated Receptor-γ Activation Induces 11β-Hydroxysteroid Dehydrogenase Type 1 Activity in Human Alternative Macrophages.
MedLine Citation:
PMID:  22207732     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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. CONCLUSIONS: Our data identify a positive cross-talk between PPARγ and GR in human M2 macrophages via the induction of 11β-HSD1 expression and activity.
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
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-29
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  -     ISSN:  1524-4636     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Université Lille Nord de France, Lille, France.
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