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Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ

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 acti...

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Autores principales: Rousseaux, Christel, Lefebvre, Bruno, Dubuquoy, Laurent, Lefebvre, Philippe, Romano, Olivier, Auwerx, Johan, Metzger, Daniel, Wahli, Walter, Desvergne, Béatrice, Naccari, Gian Carlo, Chavatte, Philippe, Farce, Amaury, Bulois, Philippe, Cortot, Antoine, Colombel, Jean Frédéric, Desreumaux, Pierre
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213148/
https://www.ncbi.nlm.nih.gov/pubmed/15824083
http://dx.doi.org/10.1084/jem.20041948
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author Rousseaux, Christel
Lefebvre, Bruno
Dubuquoy, Laurent
Lefebvre, Philippe
Romano, Olivier
Auwerx, Johan
Metzger, Daniel
Wahli, Walter
Desvergne, Béatrice
Naccari, Gian Carlo
Chavatte, Philippe
Farce, Amaury
Bulois, Philippe
Cortot, Antoine
Colombel, Jean Frédéric
Desreumaux, Pierre
author_facet Rousseaux, Christel
Lefebvre, Bruno
Dubuquoy, Laurent
Lefebvre, Philippe
Romano, Olivier
Auwerx, Johan
Metzger, Daniel
Wahli, Walter
Desvergne, Béatrice
Naccari, Gian Carlo
Chavatte, Philippe
Farce, Amaury
Bulois, Philippe
Cortot, Antoine
Colombel, Jean Frédéric
Desreumaux, Pierre
author_sort Rousseaux, Christel
collection PubMed
description 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-γ (PPAR-γ) 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-γ(+/−) 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-γ 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-γ as a target of 5-ASA underlying antiinflammatory effects in the colon.
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spelling pubmed-22131482008-03-11 Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ Rousseaux, Christel Lefebvre, Bruno Dubuquoy, Laurent Lefebvre, Philippe Romano, Olivier Auwerx, Johan Metzger, Daniel Wahli, Walter Desvergne, Béatrice Naccari, Gian Carlo Chavatte, Philippe Farce, Amaury Bulois, Philippe Cortot, Antoine Colombel, Jean Frédéric Desreumaux, Pierre J Exp Med Article 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-γ (PPAR-γ) 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-γ(+/−) 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-γ 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-γ as a target of 5-ASA underlying antiinflammatory effects in the colon. The Rockefeller University Press 2005-04-18 /pmc/articles/PMC2213148/ /pubmed/15824083 http://dx.doi.org/10.1084/jem.20041948 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Rousseaux, Christel
Lefebvre, Bruno
Dubuquoy, Laurent
Lefebvre, Philippe
Romano, Olivier
Auwerx, Johan
Metzger, Daniel
Wahli, Walter
Desvergne, Béatrice
Naccari, Gian Carlo
Chavatte, Philippe
Farce, Amaury
Bulois, Philippe
Cortot, Antoine
Colombel, Jean Frédéric
Desreumaux, Pierre
Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ
title Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ
title_full Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ
title_fullStr Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ
title_full_unstemmed Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ
title_short Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ
title_sort intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213148/
https://www.ncbi.nlm.nih.gov/pubmed/15824083
http://dx.doi.org/10.1084/jem.20041948
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