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5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium

5-Aminosalicylic acid (5-ASA), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, is a widely used first-line medication for the treatment of ulcerative colitis, but its anti-inflammatory mechanism is not fully resolved. Here, we show that 5-ASA ameliorates colitis in dextran sulfa...

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Detalles Bibliográficos
Autores principales: Cevallos, Stephanie A., Lee, Jee-Yon, Velazquez, Eric M., Foegeding, Nora J., Shelton, Catherine D., Tiffany, Connor R., Parry, Beau H., Stull-Lane, Annica R., Olsan, Erin E., Savage, Hannah P., Nguyen, Henry, Ghanaat, Star S., Byndloss, Austin J., Agu, Ilechukwu O., Tsolis, Renée M., Byndloss, Mariana X., Bäumler, Andreas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845635/
https://www.ncbi.nlm.nih.gov/pubmed/33468700
http://dx.doi.org/10.1128/mBio.03227-20
Descripción
Sumario:5-Aminosalicylic acid (5-ASA), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, is a widely used first-line medication for the treatment of ulcerative colitis, but its anti-inflammatory mechanism is not fully resolved. Here, we show that 5-ASA ameliorates colitis in dextran sulfate sodium (DSS)-treated mice by activating PPAR-γ signaling in the intestinal epithelium. DSS-induced colitis was associated with a loss of epithelial hypoxia and a respiration-dependent luminal expansion of Escherichia coli, which could be ameliorated by treatment with 5-ASA. However, 5-ASA was no longer able to reduce inflammation, restore epithelial hypoxia, or blunt an expansion of E. coli in DSS-treated mice that lacked Pparg expression specifically in the intestinal epithelium. These data suggest that the anti-inflammatory activity of 5-ASA requires activation of epithelial PPAR-γ signaling, thus pointing to the intestinal epithelium as a potential target for therapeutic intervention in ulcerative colitis.