Cargando…
Interferon-γ Suppresses Intestinal Epithelial Aquaporin-1 Expression via Janus Kinase and STAT3 Activation
Inflammatory bowel diseases are associated with dysregulated electrolyte and water transport and resultant diarrhea. Aquaporins are transmembrane proteins that function as water channels in intestinal epithelial cells. We investigated the effect of the inflammatory cytokine, interferon-γ, which is a...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405000/ https://www.ncbi.nlm.nih.gov/pubmed/25793528 http://dx.doi.org/10.1371/journal.pone.0118713 |
_version_ | 1782367583387779072 |
---|---|
author | Dicay, Michael S. Hirota, Christina L. Ronaghan, Natalie J. Peplowski, Michael A. Zaheer, Raza S. Carati, Colin A. MacNaughton, Wallace K. |
author_facet | Dicay, Michael S. Hirota, Christina L. Ronaghan, Natalie J. Peplowski, Michael A. Zaheer, Raza S. Carati, Colin A. MacNaughton, Wallace K. |
author_sort | Dicay, Michael S. |
collection | PubMed |
description | Inflammatory bowel diseases are associated with dysregulated electrolyte and water transport and resultant diarrhea. Aquaporins are transmembrane proteins that function as water channels in intestinal epithelial cells. We investigated the effect of the inflammatory cytokine, interferon-γ, which is a major player in inflammatory bowel diseases, on aquaporin-1 expression in a mouse colonic epithelial cell line, CMT93. CMT93 monolayers were exposed to 10 ng/mL interferon-γ and aquaporin-1 mRNA and protein expressions were measured by real-time PCR and western blot, respectively. In other experiments, CMT93 cells were pretreated with inhibitors or were transfected with siRNA to block the effects of Janus kinases, STATs 1 and 3, or interferon regulatory factor 2, prior to treatment with interferon-γ. Interferon-γ decreased aquaporin-1 expression in mouse intestinal epithelial cells in a manner that did not depend on the classical STAT1/JAK2/IRF-1 pathway, but rather, on an alternate Janus kinase (likely JAK1) as well as on STAT3. The pro-inflammatory cytokine, interferon-γ may contribute to diarrhea associated with intestinal inflammation in part through regulation of the epithelial aquaporin-1 water channel via a non-classical JAK/STAT receptor signalling pathway. |
format | Online Article Text |
id | pubmed-4405000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44050002015-05-02 Interferon-γ Suppresses Intestinal Epithelial Aquaporin-1 Expression via Janus Kinase and STAT3 Activation Dicay, Michael S. Hirota, Christina L. Ronaghan, Natalie J. Peplowski, Michael A. Zaheer, Raza S. Carati, Colin A. MacNaughton, Wallace K. PLoS One Research Article Inflammatory bowel diseases are associated with dysregulated electrolyte and water transport and resultant diarrhea. Aquaporins are transmembrane proteins that function as water channels in intestinal epithelial cells. We investigated the effect of the inflammatory cytokine, interferon-γ, which is a major player in inflammatory bowel diseases, on aquaporin-1 expression in a mouse colonic epithelial cell line, CMT93. CMT93 monolayers were exposed to 10 ng/mL interferon-γ and aquaporin-1 mRNA and protein expressions were measured by real-time PCR and western blot, respectively. In other experiments, CMT93 cells were pretreated with inhibitors or were transfected with siRNA to block the effects of Janus kinases, STATs 1 and 3, or interferon regulatory factor 2, prior to treatment with interferon-γ. Interferon-γ decreased aquaporin-1 expression in mouse intestinal epithelial cells in a manner that did not depend on the classical STAT1/JAK2/IRF-1 pathway, but rather, on an alternate Janus kinase (likely JAK1) as well as on STAT3. The pro-inflammatory cytokine, interferon-γ may contribute to diarrhea associated with intestinal inflammation in part through regulation of the epithelial aquaporin-1 water channel via a non-classical JAK/STAT receptor signalling pathway. Public Library of Science 2015-03-20 /pmc/articles/PMC4405000/ /pubmed/25793528 http://dx.doi.org/10.1371/journal.pone.0118713 Text en © 2015 Dicay et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Dicay, Michael S. Hirota, Christina L. Ronaghan, Natalie J. Peplowski, Michael A. Zaheer, Raza S. Carati, Colin A. MacNaughton, Wallace K. Interferon-γ Suppresses Intestinal Epithelial Aquaporin-1 Expression via Janus Kinase and STAT3 Activation |
title | Interferon-γ Suppresses Intestinal Epithelial Aquaporin-1
Expression via Janus Kinase and STAT3 Activation |
title_full | Interferon-γ Suppresses Intestinal Epithelial Aquaporin-1
Expression via Janus Kinase and STAT3 Activation |
title_fullStr | Interferon-γ Suppresses Intestinal Epithelial Aquaporin-1
Expression via Janus Kinase and STAT3 Activation |
title_full_unstemmed | Interferon-γ Suppresses Intestinal Epithelial Aquaporin-1
Expression via Janus Kinase and STAT3 Activation |
title_short | Interferon-γ Suppresses Intestinal Epithelial Aquaporin-1
Expression via Janus Kinase and STAT3 Activation |
title_sort | interferon-γ suppresses intestinal epithelial aquaporin-1
expression via janus kinase and stat3 activation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405000/ https://www.ncbi.nlm.nih.gov/pubmed/25793528 http://dx.doi.org/10.1371/journal.pone.0118713 |
work_keys_str_mv | AT dicaymichaels interferongsuppressesintestinalepithelialaquaporin1expressionviajanuskinaseandstat3activation AT hirotachristinal interferongsuppressesintestinalepithelialaquaporin1expressionviajanuskinaseandstat3activation AT ronaghannataliej interferongsuppressesintestinalepithelialaquaporin1expressionviajanuskinaseandstat3activation AT peplowskimichaela interferongsuppressesintestinalepithelialaquaporin1expressionviajanuskinaseandstat3activation AT zaheerrazas interferongsuppressesintestinalepithelialaquaporin1expressionviajanuskinaseandstat3activation AT caraticolina interferongsuppressesintestinalepithelialaquaporin1expressionviajanuskinaseandstat3activation AT macnaughtonwallacek interferongsuppressesintestinalepithelialaquaporin1expressionviajanuskinaseandstat3activation |