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Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells
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A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response

C G Su1, X Wen, S T Bailey

  • 1Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

The Journal of Clinical Investigation
|August 17, 1999
PubMed

Insights

PPAR-gamma ligands reduce inflammatory cytokine gene expression and colonic inflammation. This suggests targeting PPAR-gamma (peroxisome proliferator-activated receptor gamma) could be a therapeutic strategy for inflammatory bowel disease (IBD).

Area of Science:

  • Molecular Biology
  • Immunology
  • Gastroenterology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is involved in adipocyte differentiation, glucose homeostasis, cellular proliferation, and inflammation.
  • Colonic epithelial cells express PPAR-gamma and produce inflammatory cytokines implicated in inflammatory bowel disease (IBD).

Purpose of the Study:

  • To investigate the role of PPAR-gamma ligands in regulating cytokine gene expression and colonic inflammation.
  • To explore PPAR-gamma as a potential therapeutic target for IBD.

Main Methods:

  • Treatment of colon cancer cell lines with PPAR-gamma ligands.
  • Analysis of cytokine gene expression and nuclear factor-kappaB (NF-kappaB) activation.
  • Administration of thiazolidinedione ligands to a mouse model of IBD.

Main Results:

  • PPAR-gamma ligands significantly attenuated cytokine gene expression in colon cancer cells.
  • Inhibition of NF-kappaB activation via an IkappaB-alpha-dependent mechanism was observed.
  • Thiazolidinedione ligands markedly reduced colonic inflammation in the IBD mouse model.

Conclusions:

  • Colonic PPAR-gamma plays a crucial role in regulating inflammatory responses.
  • PPAR-gamma ligands demonstrate therapeutic potential for treating IBD.
  • Targeting colonic PPAR-gamma may offer a novel strategy for managing inflammatory bowel disease.

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