STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells

Immunity. 2010 Nov 24;33(5):699-712. doi: 10.1016/j.immuni.2010.11.009.

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a lipid-activated transcription factor regulating lipid metabolism and inflammatory response in macrophages and dendritic cells (DCs). These immune cells exposed to distinct inflammatory milieu show cell type specification as a result of altered gene expression. We demonstrate here a mechanism how inflammatory molecules modulate PPARγ signaling in distinct subsets of cells. Proinflammatory molecules inhibited whereas interleukin-4 (IL-4) stimulated PPARγ activity in macrophages and DCs. Furthermore, IL-4 signaling augmented PPARγ activity through an interaction between PPARγ and signal transducer and activators of transcription 6 (STAT6) on promoters of PPARγ target genes, including FABP4. Thus, STAT6 acts as a facilitating factor for PPARγ by promoting DNA binding and consequently increasing the number of regulated genes and the magnitude of responses. This interaction, underpinning cell type-specific responses, represents a unique way of controlling nuclear receptor signaling by inflammatory molecules in immune cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells / metabolism*
  • Fatty Acid-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-4 / metabolism
  • Macrophages / metabolism*
  • Mice
  • PPAR gamma / metabolism*
  • Promoter Regions, Genetic
  • STAT6 Transcription Factor / metabolism*

Substances

  • FABP4 protein, human
  • Fabp4 protein, mouse
  • Fatty Acid-Binding Proteins
  • Inflammation Mediators
  • PPAR gamma
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Stat6 protein, mouse
  • Interleukin-4

Associated data

  • GEO/GSE16387