Diagenode

>>>   Click for Diagenode’s approach to COVID-19

The transcriptional PPARβ/δ network in human macrophages defines a unique agonist-induced activation state.


Adhikary T, Wortmann A, Schumann T, Finkernagel F, Lieber S, Roth K, Toth PM, Diederich WE, Nist A, Stiewe T, Kleinesudeik L, Reinartz S, Müller-Brüsselbach S, Müller R

Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a lipid ligand-inducible transcription factor with established metabolic functions, whereas its anti-inflammatory function is poorly understood. To address this issue, we determined the global PPARβ/δ-regulated signaling network in human monocyte-derived macrophages. Besides cell type-independent, canonical target genes with metabolic and immune regulatory functions we identified a large number of inflammation-associated NFκB and STAT1 target genes that are repressed by agonists. Accordingly, PPARβ/δ agonists inhibited the expression of multiple pro-inflammatory mediators and induced an anti-inflammatory, IL-4-like morphological phenotype. Surprisingly, bioinformatic analyses also identified immune stimulatory effects. Consistent with this prediction, PPARβ/δ agonists enhanced macrophage survival under hypoxic stress and stimulated CD8(+) T cell activation, concomitantly with the repression of immune suppressive target genes and their encoded products CD274 (PD-1 ligand), CD32B (inhibitory Fcγ receptor IIB) and indoleamine 2,3-dioxygenase 1 (IDO-1), as well as a diminished release of the immune suppressive IDO-1 metabolite kynurenine. Comparison with published data revealed a significant overlap of the PPARβ/δ transcriptome with coexpression modules characteristic of both anti-inflammatory and pro-inflammatory cytokines. Our findings indicate that PPARβ/δ agonists induce a unique macrophage activation state with strong anti-inflammatory but also specific immune stimulatory components, pointing to a context-dependent function of PPARβ/δ in immune regulation.

Tags
Microplex Library Preparation kit

Share this article

Published
May, 2015

Source

Events

  • ChIP workshop
    Diagenode
    Sep 21-Sep 22, 2021
  • DNA methylation workshop: Master MeDIP assay
    Diagenode
    Sep 30, 2021
  • DNA methylation workshop: Become an expert at RRBS
    Diagenode
    Oct 1-Oct 31, 2021
 See all events

News

 See all news


The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.



  ABOUT SSL CERTIFICATES

       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics