Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783644593870340096 |
---|---|
author | 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. |
author_facet | 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. |
author_sort | Cevallos, Stephanie A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7845635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-78456352021-02-05 5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium 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. mBio Research Article 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. American Society for Microbiology 2021-01-19 /pmc/articles/PMC7845635/ /pubmed/33468700 http://dx.doi.org/10.1128/mBio.03227-20 Text en Copyright © 2021 Cevallos et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article 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. 5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium |
title | 5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium |
title_full | 5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium |
title_fullStr | 5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium |
title_full_unstemmed | 5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium |
title_short | 5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium |
title_sort | 5-aminosalicylic acid ameliorates colitis and checks dysbiotic escherichia coli expansion by activating ppar-γ signaling in the intestinal epithelium |
topic | Research Article |
url | 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 |
work_keys_str_mv | AT cevallosstephaniea 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT leejeeyon 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT velazquezericm 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT foegedingnoraj 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT sheltoncatherined 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT tiffanyconnorr 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT parrybeauh 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT stulllaneannicar 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT olsanerine 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT savagehannahp 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT nguyenhenry 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT ghanaatstars 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT byndlossaustinj 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT aguilechukwuo 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT tsolisreneem 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT byndlossmarianax 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium AT baumlerandreasj 5aminosalicylicacidamelioratescolitisandchecksdysbioticescherichiacoliexpansionbyactivatingppargsignalingintheintestinalepithelium |