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Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent-invasive Escherichia coli invasion
BACKGROUND AND AIMS: Crohn's disease (CD) ileal lesions are colonised by pathogenic adherent-invasive Escherichia coli (AIEC) producing outer membrane vesicles (OMVs) that contribute to the bacterial invasion process. In addition, increased expression of endoplasmic reticulum (ER)-localised str...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BMJ Group
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976078/ https://www.ncbi.nlm.nih.gov/pubmed/20587550 http://dx.doi.org/10.1136/gut.2010.207456 |
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author | Rolhion, Nathalie Barnich, Nicolas Bringer, Marie-Agnès Glasser, Anne-Lise Ranc, Julien Hébuterne, Xavier Hofman, Paul Darfeuille-Michaud, Arlette |
author_facet | Rolhion, Nathalie Barnich, Nicolas Bringer, Marie-Agnès Glasser, Anne-Lise Ranc, Julien Hébuterne, Xavier Hofman, Paul Darfeuille-Michaud, Arlette |
author_sort | Rolhion, Nathalie |
collection | PubMed |
description | BACKGROUND AND AIMS: Crohn's disease (CD) ileal lesions are colonised by pathogenic adherent-invasive Escherichia coli (AIEC) producing outer membrane vesicles (OMVs) that contribute to the bacterial invasion process. In addition, increased expression of endoplasmic reticulum (ER)-localised stress response proteins, due to ER stress, is observed in patients with CD. The expression of the ER-localised stress response protein Gp96 in patients with CD and its biological role with regards to the ability of AIEC to invade intestinal epithelial cells were analysed. METHODS AND RESULTS: Immunohistochemistry on tissue arrays showed that, together with CEACAM6 (carcinoembryonic antigen-related cell adhesion molecule 6) or the ER stress protein Grp78, Gp96 is also strongly expressed at the apical plasma membrane of the ileal epithelial cells of 50% of patients with CD. Invasion experiments in the presence of antibodies raised against Gp96, or after transfection of Intestine-407 cells with gp96 small interfering RNA (siRNA), indicated that Gp96 is essential to promote AIEC LF82 invasion, allowing, via the recognition of the outer membrane protein OmpA, OMVs to fuse with intestinal epithelial cells. CONCLUSIONS: Gp96 is overexpressed on the apical surface of ileal epithelial cells in patients with CD and acts as a host cell receptor for OMVs, promoting AIEC invasion. From the results shown here, it is speculated that AIEC could take advantage of the abnormal expression of Gp96 in patients with CD to invade the ileal mucosa. |
format | Text |
id | pubmed-2976078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BMJ Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-29760782010-11-26 Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent-invasive Escherichia coli invasion Rolhion, Nathalie Barnich, Nicolas Bringer, Marie-Agnès Glasser, Anne-Lise Ranc, Julien Hébuterne, Xavier Hofman, Paul Darfeuille-Michaud, Arlette Gut Inflammatory Bowel Disease BACKGROUND AND AIMS: Crohn's disease (CD) ileal lesions are colonised by pathogenic adherent-invasive Escherichia coli (AIEC) producing outer membrane vesicles (OMVs) that contribute to the bacterial invasion process. In addition, increased expression of endoplasmic reticulum (ER)-localised stress response proteins, due to ER stress, is observed in patients with CD. The expression of the ER-localised stress response protein Gp96 in patients with CD and its biological role with regards to the ability of AIEC to invade intestinal epithelial cells were analysed. METHODS AND RESULTS: Immunohistochemistry on tissue arrays showed that, together with CEACAM6 (carcinoembryonic antigen-related cell adhesion molecule 6) or the ER stress protein Grp78, Gp96 is also strongly expressed at the apical plasma membrane of the ileal epithelial cells of 50% of patients with CD. Invasion experiments in the presence of antibodies raised against Gp96, or after transfection of Intestine-407 cells with gp96 small interfering RNA (siRNA), indicated that Gp96 is essential to promote AIEC LF82 invasion, allowing, via the recognition of the outer membrane protein OmpA, OMVs to fuse with intestinal epithelial cells. CONCLUSIONS: Gp96 is overexpressed on the apical surface of ileal epithelial cells in patients with CD and acts as a host cell receptor for OMVs, promoting AIEC invasion. From the results shown here, it is speculated that AIEC could take advantage of the abnormal expression of Gp96 in patients with CD to invade the ileal mucosa. BMJ Group 2010-06-29 2010-10 /pmc/articles/PMC2976078/ /pubmed/20587550 http://dx.doi.org/10.1136/gut.2010.207456 Text en © 2010, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode. |
spellingShingle | Inflammatory Bowel Disease Rolhion, Nathalie Barnich, Nicolas Bringer, Marie-Agnès Glasser, Anne-Lise Ranc, Julien Hébuterne, Xavier Hofman, Paul Darfeuille-Michaud, Arlette Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent-invasive Escherichia coli invasion |
title | Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent-invasive Escherichia coli invasion |
title_full | Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent-invasive Escherichia coli invasion |
title_fullStr | Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent-invasive Escherichia coli invasion |
title_full_unstemmed | Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent-invasive Escherichia coli invasion |
title_short | Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent-invasive Escherichia coli invasion |
title_sort | abnormally expressed er stress response chaperone gp96 in cd favours adherent-invasive escherichia coli invasion |
topic | Inflammatory Bowel Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976078/ https://www.ncbi.nlm.nih.gov/pubmed/20587550 http://dx.doi.org/10.1136/gut.2010.207456 |
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