Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator-activated receptor-gamma. - Archive ouverte HAL Access content directly
Journal Articles Journal of Experimental Medicine Year : 2005

Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator-activated receptor-gamma.

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1
Christel Rousseaux
  • Function : Author
Bruno Lefebvre
  • Function : Author
Philippe Lefebvre
  • Function : Author
Olivier Romano
  • Function : Author
Walter Wahli
  • Function : Author
Béatrice Desvergne
  • Function : Author
Gian Carlo Naccari
  • Function : Author
Philippe Chavatte
  • Function : Author
Amaury Farce
  • Function : Author
Philippe Bulois
  • Function : Author
Antoine Cortot
  • Function : Author
Jean Frédéric Colombel
  • Function : Author
Pierre Desreumaux
  • Function : Author

Abstract

5-aminosalicylic acid (5-ASA) is an antiinflammatory drug widely used in the treatment of inflammatory bowel diseases. It is known to inhibit the production of cytokines and inflammatory mediators, but the mechanism underlying the intestinal effects of 5-ASA remains unknown. Based on the common activities of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands and 5-ASA, we hypothesized that this nuclear receptor mediates 5-ASA therapeutic action. To test this possibility, colitis was induced in heterozygous PPAR-gamma(+/-) mice and their wild-type littermates, which were then treated with 5-ASA. 5-ASA treatment had a beneficial effect on colitis only in wild-type and not in heterozygous mice. In epithelial cells, 5-ASA increased PPAR-gamma expression, promoted its translocation from the cytoplasm to the nucleus, and induced a modification of its conformation permitting the recruitment of coactivators and the activation of a peroxisome-proliferator response element-driven gene. Validation of these results was obtained with organ cultures of human colonic biopsies. These data identify PPAR-gamma as a target of 5-ASA underlying antiinflammatory effects in the colon.

Dates and versions

hal-00187736 , version 1 (15-11-2007)

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Christel Rousseaux, Bruno Lefebvre, Laurent Dubuquoy, Philippe Lefebvre, Olivier Romano, et al.. Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator-activated receptor-gamma.. Journal of Experimental Medicine, 2005, 201 (8), pp.1205-15. ⟨10.1084/jem.20041948⟩. ⟨hal-00187736⟩
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