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STAT6 Signaling Mediates PPARγ Activation and Resolution of Acute Sterile Inflammation in Mice

Ye-Ji Lee1,2, Bo-Min Kim1,2, Young-Ho Ahn2,3

  • 1Department of Physiology, College of Medicine, Ewha Womans University, Seoul 07804, Korea.

Cells
|March 3, 2021
PubMed

Insights

Signal transducer and activator of transcription 6 (STAT6) enhances peroxisome proliferator-activated receptor gamma (PPARγ) activation in macrophages, promoting inflammation resolution and efferocytosis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Inflammation Research

Background:

  • Signal transducer and activator of transcription 6 (STAT6) is known to activate the peroxisome proliferator-activated receptor gamma (PPARγ) pathway in macrophages.
  • The precise role of STAT6 signaling in PPARγ activation and its impact on resolving acute inflammation remain largely uncharacterized.

Purpose of the Study:

  • To investigate the function of STAT6 signaling in PPARγ activation during the resolution of acute sterile inflammation.
  • To elucidate the role of STAT6 in modulating inflammatory responses and efferocytosis in a murine model of zymosan-induced peritonitis.

Main Methods:

  • Utilized a murine model of zymosan-induced peritonitis.
  • Compared wild-type (WT) mice with STAT6-deficient mice.
  • Analyzed peritoneal lavage fluid (PLF) and serum for cytokine levels, neutrophil counts, and protein content; assessed PPARγ expression and efferocytosis in peritoneal macrophages.

Main Results:

  • STAT6 deficiency exacerbated zymosan-induced pro-inflammatory cytokine production (TNF-α, IL-6, MIP-2) and neutrophil infiltration.
  • STAT6 deficiency led to reduced levels of pro-resolving molecules (IL-10, HGF) and impaired efferocytosis by macrophages.
  • STAT6-deficient macrophages and spleens showed lower expression of PPARγ and its target genes compared to WT mice.

Conclusions:

  • STAT6 signaling is crucial for PPARγ activation and macrophage programming during inflammation resolution.
  • Enhanced STAT6 activity promotes efferocytosis and contributes to the resolution of acute sterile inflammation.
  • STAT6 deficiency impairs the resolution of inflammation by downregulating PPARγ-mediated pathways.
Keywords:
PPARγSTAT6efferocytosismacrophagesresolution of inflammation

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