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

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

Research output: Contribution to journalArticlepeer-review

Abstract

Objective-11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) catalyzes the intracellular reduction of inactive cortisone to active cortisol, the natural ligand activating the glucocorticoid receptor (GR). Peroxisome proliferator-activated receptor-gamma (PPAR gamma) 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 11 beta-HSD1 and the role of PPAR gamma therein.

Methods and Results-11 beta-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, PPAR gamma activation induces 11 beta-HSD1 enzyme activity in M2 macrophages but not in resting macrophages or M1 macrophages. Consequently, human M2 macrophages displayed enhanced responsiveness to the 11 beta-HSD1 substrate cortisone, an effect amplified by PPAR gamma induction of 11 beta-HSD1 activity, as illustrated by an increased expression of GR target genes.

Conclusion-Our data identify a positive cross-talk between PPAR gamma and GR in human M2 macrophages via the induction of 11 beta-HSD1 expression and activity. (Arterioscler Thromb Vasc Biol. 2012;32:677-685.)

Original languageEnglish
Pages (from-to)677-U342
Number of pages16
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume32
Issue number3
DOIs
Publication statusPublished - Mar 2012

Keywords

  • Macrophages
  • Hydrocortisone
  • Cortisone
  • Humans
  • Thiazolidinediones
  • Receptors, Glucocorticoid
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Inflammation
  • Transfection
  • Cells, Cultured
  • Interleukin-4
  • Genes, Reporter
  • PPAR gamma
  • Enzyme Induction
  • RNA Interference
  • Time Factors

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