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

Attila Szanto, Balint L. Balint, Zsuzsanna S. Nagy, E. Barta, B. Dezső, Attila Pap, L. Széles, Szilard Poliska, Melinda Oros, Ronald M. Evans, Yaacov Barak, John Schwabe, L. Nagy

Research output: Contribution to journalArticle

202 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)699-712
Number of pages14
JournalImmunity
Volume33
Issue number5
DOIs
Publication statusPublished - Nov 24 2010

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STAT6 Transcription Factor
Peroxisome Proliferator-Activated Receptors
Cytoplasmic and Nuclear Receptors
Dendritic Cells
Transcription Factors
Macrophages
Gene Expression
Interleukin-4
Lipid Metabolism
Cell Communication
Genes
Lipids
DNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells. / Szanto, Attila; Balint, Balint L.; Nagy, Zsuzsanna S.; Barta, E.; Dezső, B.; Pap, Attila; Széles, L.; Poliska, Szilard; Oros, Melinda; Evans, Ronald M.; Barak, Yaacov; Schwabe, John; Nagy, L.

In: Immunity, Vol. 33, No. 5, 24.11.2010, p. 699-712.

Research output: Contribution to journalArticle

Szanto, Attila ; Balint, Balint L. ; Nagy, Zsuzsanna S. ; Barta, E. ; Dezső, B. ; Pap, Attila ; Széles, L. ; Poliska, Szilard ; Oros, Melinda ; Evans, Ronald M. ; Barak, Yaacov ; Schwabe, John ; Nagy, L. / STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells. In: Immunity. 2010 ; Vol. 33, No. 5. pp. 699-712.
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AU - Dezső, B.

AU - Pap, Attila

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AU - Poliska, Szilard

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AU - Evans, Ronald M.

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