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Peroxisome proliferator-activated receptor gamma agonist ligands stimulate a Th2 cytokine response and prevent acute

Lawrence J Saubermann1, Atsushi Nakajima, Koichiro Wada

  • 1lawrence.saubermann@bmc.org

Inflammatory Bowel Diseases
|December 14, 2002
PubMed

Insights

Activation of Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands before colitis onset protects against intestinal inflammation. This protection involves shifting the immune response from Th1 to Th2 cytokine dominance.

Area of Science:

  • Immunology
  • Molecular Biology
  • Gastroenterology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor with known anti-inflammatory properties.
  • The role of PPARgamma activation in immune response modulation, particularly in inflammatory conditions like colitis, requires further elucidation.

Purpose of the Study:

  • To investigate the immunologic effects of PPARgamma activation in a dextran sodium sulfate (DSS)-induced colitis model.
  • To determine if PPARgamma activation influences susceptibility and severity of experimental colitis.

Main Methods:

  • Evaluation of PPARgamma heterozygote (PPARgamma(+/-)) mice and wild-type littermates in a DSS-induced colitis model.
  • Administration of specific PPARgamma ligands (troglitazone, pioglitazone, rosiglitazone) before and after colitis onset.
  • Assessment of clinical and histological parameters, and measurement of cytokine profiles (IFN-γ, TNF-α, IL-4, IL-10) and GATA-3 expression via quantitative RT-PCR.

Main Results:

  • PPARgamma(+/-) mice exhibited increased susceptibility to DSS-induced colitis.
  • Pre-treatment with PPARgamma ligands conferred dose-dependent protection against colitis, evidenced by improved body weight, reduced histological injury, and enhanced survival.
  • Post-treatment with PPARgamma ligands did not provide protection.
  • Ligand treatment led to decreased Th1 cytokines (IFN-γ, TNF-α) and increased Th2 cytokines (IL-4, IL-10), along with elevated GATA-3 expression, indicating a shift towards Th2 immunity.

Conclusions:

  • PPARgamma activation plays a crucial role in modulating immune responses during intestinal inflammation.
  • Pre-emptive PPARgamma ligand administration can protect against experimental colitis by promoting a Th2-dominant immune profile.
  • Targeting PPARgamma may represent a therapeutic strategy for inflammatory bowel diseases, contingent on appropriate timing of intervention.

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