Cargando…
JAM-A regulates permeability and inflammation in the intestine in vivo
Recent evidence has linked intestinal permeability to mucosal inflammation, but molecular studies are lacking. Candidate regulatory molecules localized within the tight junction (TJ) include Junctional Adhesion Molecule (JAM-A), which has been implicated in the regulation of barrier function and leu...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2007
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150975/ https://www.ncbi.nlm.nih.gov/pubmed/18039951 http://dx.doi.org/10.1084/jem.20071416 |
_version_ | 1782144682274324480 |
---|---|
author | Laukoetter, Mike G. Nava, Porfirio Lee, Winston Y. Severson, Eric A. Capaldo, Christopher T. Babbin, Brian A. Williams, Ifor R. Koval, Michael Peatman, Eric Campbell, Jacquelyn A. Dermody, Terence S. Nusrat, Asma Parkos, Charles A. |
author_facet | Laukoetter, Mike G. Nava, Porfirio Lee, Winston Y. Severson, Eric A. Capaldo, Christopher T. Babbin, Brian A. Williams, Ifor R. Koval, Michael Peatman, Eric Campbell, Jacquelyn A. Dermody, Terence S. Nusrat, Asma Parkos, Charles A. |
author_sort | Laukoetter, Mike G. |
collection | PubMed |
description | Recent evidence has linked intestinal permeability to mucosal inflammation, but molecular studies are lacking. Candidate regulatory molecules localized within the tight junction (TJ) include Junctional Adhesion Molecule (JAM-A), which has been implicated in the regulation of barrier function and leukocyte migration. Thus, we analyzed the intestinal mucosa of JAM-A–deficient (JAM-A(−/−)) mice for evidence of enhanced permeability and inflammation. Colonic mucosa from JAM-A(−/−) mice had normal epithelial architecture but increased polymorphonuclear leukocyte infiltration and large lymphoid aggregates not seen in wild-type controls. Barrier function experiments revealed increased mucosal permeability, as indicated by enhanced dextran flux, and decreased transepithelial electrical resistance in JAM-A(−/−) mice. The in vivo observations were epithelial specific, because monolayers of JAM-A(−/−) epithelial cells also demonstrated increased permeability. Analyses of other TJ components revealed increased expression of claudin-10 and -15 in the colonic mucosa of JAM-A(−/−) mice and in JAM-A small interfering RNA–treated epithelial cells. Given the observed increase in colonic inflammation and permeability, we assessed the susceptibility of JAM-A(−/−) mice to the induction of colitis with dextran sulfate sodium (DSS). Although DSS-treated JAM-A(−/−) animals had increased clinical disease compared with controls, colonic mucosa showed less injury and increased epithelial proliferation. These findings demonstrate a complex role of JAM-A in intestinal homeostasis by regulating epithelial permeability, inflammation, and proliferation. |
format | Text |
id | pubmed-2150975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21509752008-06-24 JAM-A regulates permeability and inflammation in the intestine in vivo Laukoetter, Mike G. Nava, Porfirio Lee, Winston Y. Severson, Eric A. Capaldo, Christopher T. Babbin, Brian A. Williams, Ifor R. Koval, Michael Peatman, Eric Campbell, Jacquelyn A. Dermody, Terence S. Nusrat, Asma Parkos, Charles A. J Exp Med Brief Definitive Reports Recent evidence has linked intestinal permeability to mucosal inflammation, but molecular studies are lacking. Candidate regulatory molecules localized within the tight junction (TJ) include Junctional Adhesion Molecule (JAM-A), which has been implicated in the regulation of barrier function and leukocyte migration. Thus, we analyzed the intestinal mucosa of JAM-A–deficient (JAM-A(−/−)) mice for evidence of enhanced permeability and inflammation. Colonic mucosa from JAM-A(−/−) mice had normal epithelial architecture but increased polymorphonuclear leukocyte infiltration and large lymphoid aggregates not seen in wild-type controls. Barrier function experiments revealed increased mucosal permeability, as indicated by enhanced dextran flux, and decreased transepithelial electrical resistance in JAM-A(−/−) mice. The in vivo observations were epithelial specific, because monolayers of JAM-A(−/−) epithelial cells also demonstrated increased permeability. Analyses of other TJ components revealed increased expression of claudin-10 and -15 in the colonic mucosa of JAM-A(−/−) mice and in JAM-A small interfering RNA–treated epithelial cells. Given the observed increase in colonic inflammation and permeability, we assessed the susceptibility of JAM-A(−/−) mice to the induction of colitis with dextran sulfate sodium (DSS). Although DSS-treated JAM-A(−/−) animals had increased clinical disease compared with controls, colonic mucosa showed less injury and increased epithelial proliferation. These findings demonstrate a complex role of JAM-A in intestinal homeostasis by regulating epithelial permeability, inflammation, and proliferation. The Rockefeller University Press 2007-12-24 /pmc/articles/PMC2150975/ /pubmed/18039951 http://dx.doi.org/10.1084/jem.20071416 Text en Copyright © 2007, 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 | Brief Definitive Reports Laukoetter, Mike G. Nava, Porfirio Lee, Winston Y. Severson, Eric A. Capaldo, Christopher T. Babbin, Brian A. Williams, Ifor R. Koval, Michael Peatman, Eric Campbell, Jacquelyn A. Dermody, Terence S. Nusrat, Asma Parkos, Charles A. JAM-A regulates permeability and inflammation in the intestine in vivo |
title | JAM-A regulates permeability and inflammation in the intestine in vivo |
title_full | JAM-A regulates permeability and inflammation in the intestine in vivo |
title_fullStr | JAM-A regulates permeability and inflammation in the intestine in vivo |
title_full_unstemmed | JAM-A regulates permeability and inflammation in the intestine in vivo |
title_short | JAM-A regulates permeability and inflammation in the intestine in vivo |
title_sort | jam-a regulates permeability and inflammation in the intestine in vivo |
topic | Brief Definitive Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150975/ https://www.ncbi.nlm.nih.gov/pubmed/18039951 http://dx.doi.org/10.1084/jem.20071416 |
work_keys_str_mv | AT laukoettermikeg jamaregulatespermeabilityandinflammationintheintestineinvivo AT navaporfirio jamaregulatespermeabilityandinflammationintheintestineinvivo AT leewinstony jamaregulatespermeabilityandinflammationintheintestineinvivo AT seversonerica jamaregulatespermeabilityandinflammationintheintestineinvivo AT capaldochristophert jamaregulatespermeabilityandinflammationintheintestineinvivo AT babbinbriana jamaregulatespermeabilityandinflammationintheintestineinvivo AT williamsiforr jamaregulatespermeabilityandinflammationintheintestineinvivo AT kovalmichael jamaregulatespermeabilityandinflammationintheintestineinvivo AT peatmaneric jamaregulatespermeabilityandinflammationintheintestineinvivo AT campbelljacquelyna jamaregulatespermeabilityandinflammationintheintestineinvivo AT dermodyterences jamaregulatespermeabilityandinflammationintheintestineinvivo AT nusratasma jamaregulatespermeabilityandinflammationintheintestineinvivo AT parkoscharlesa jamaregulatespermeabilityandinflammationintheintestineinvivo |