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Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation

Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here,...

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Autores principales: Kurashima, Yosuke, Kigoshi, Takaaki, Murasaki, Sayuri, Arai, Fujimi, Shimada, Kaoru, Seki, Natsumi, Kim, Yun-Gi, Hase, Koji, Ohno, Hiroshi, Kawano, Kazuya, Ashida, Hiroshi, Suzuki, Toshihiko, Morimoto, Masako, Saito, Yukari, Sasou, Ai, Goda, Yuki, Yuki, Yoshikazu, Inagaki, Yutaka, Iijima, Hideki, Suda, Wataru, Hattori, Masahira, Kiyono, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887276/
https://www.ncbi.nlm.nih.gov/pubmed/33594081
http://dx.doi.org/10.1038/s41467-021-21277-2
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author Kurashima, Yosuke
Kigoshi, Takaaki
Murasaki, Sayuri
Arai, Fujimi
Shimada, Kaoru
Seki, Natsumi
Kim, Yun-Gi
Hase, Koji
Ohno, Hiroshi
Kawano, Kazuya
Ashida, Hiroshi
Suzuki, Toshihiko
Morimoto, Masako
Saito, Yukari
Sasou, Ai
Goda, Yuki
Yuki, Yoshikazu
Inagaki, Yutaka
Iijima, Hideki
Suda, Wataru
Hattori, Masahira
Kiyono, Hiroshi
author_facet Kurashima, Yosuke
Kigoshi, Takaaki
Murasaki, Sayuri
Arai, Fujimi
Shimada, Kaoru
Seki, Natsumi
Kim, Yun-Gi
Hase, Koji
Ohno, Hiroshi
Kawano, Kazuya
Ashida, Hiroshi
Suzuki, Toshihiko
Morimoto, Masako
Saito, Yukari
Sasou, Ai
Goda, Yuki
Yuki, Yoshikazu
Inagaki, Yutaka
Iijima, Hideki
Suda, Wataru
Hattori, Masahira
Kiyono, Hiroshi
author_sort Kurashima, Yosuke
collection PubMed
description Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF–dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn’s diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas–intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation.
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spelling pubmed-78872762021-03-03 Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation Kurashima, Yosuke Kigoshi, Takaaki Murasaki, Sayuri Arai, Fujimi Shimada, Kaoru Seki, Natsumi Kim, Yun-Gi Hase, Koji Ohno, Hiroshi Kawano, Kazuya Ashida, Hiroshi Suzuki, Toshihiko Morimoto, Masako Saito, Yukari Sasou, Ai Goda, Yuki Yuki, Yoshikazu Inagaki, Yutaka Iijima, Hideki Suda, Wataru Hattori, Masahira Kiyono, Hiroshi Nat Commun Article Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF–dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn’s diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas–intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation. Nature Publishing Group UK 2021-02-16 /pmc/articles/PMC7887276/ /pubmed/33594081 http://dx.doi.org/10.1038/s41467-021-21277-2 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kurashima, Yosuke
Kigoshi, Takaaki
Murasaki, Sayuri
Arai, Fujimi
Shimada, Kaoru
Seki, Natsumi
Kim, Yun-Gi
Hase, Koji
Ohno, Hiroshi
Kawano, Kazuya
Ashida, Hiroshi
Suzuki, Toshihiko
Morimoto, Masako
Saito, Yukari
Sasou, Ai
Goda, Yuki
Yuki, Yoshikazu
Inagaki, Yutaka
Iijima, Hideki
Suda, Wataru
Hattori, Masahira
Kiyono, Hiroshi
Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation
title Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation
title_full Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation
title_fullStr Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation
title_full_unstemmed Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation
title_short Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation
title_sort pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887276/
https://www.ncbi.nlm.nih.gov/pubmed/33594081
http://dx.doi.org/10.1038/s41467-021-21277-2
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