Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.

Helicobacter pylori are responsible for the induction of chronic gastric inflammation progressing to atrophy, metaplasia, and gastric cancer. The overexpression of Cathepsin X/Z (Ctsz) in H. pylori-infected mucosa and gastric cancer is mediated predominantly by an augmented migration of ctsz(-/-)pos...

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Main Authors:	Sabine Krueger, Anja Bernhardt, Thomas Kalinski, Martin Baldensperger, Michael Zeh, Anne Teller, Daniela Adolf, Thomas Reinheckel, Albert Roessner, Doerthe Kuester
Format:	article
Language:	EN
Published:	Public Library of Science (PLoS) 2013
Subjects:	Medicine R Science Q
Online Access:	https://doaj.org/article/612aaf29cdcb401cb9bdc5d0d3f564a3
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spelling	oai:doaj.org-article:612aaf29cdcb401cb9bdc5d0d3f564a32021-11-18T09:01:59ZInduction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.1932-620310.1371/journal.pone.0070242https://doaj.org/article/612aaf29cdcb401cb9bdc5d0d3f564a32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936173/?tool=EBIhttps://doaj.org/toc/1932-6203Helicobacter pylori are responsible for the induction of chronic gastric inflammation progressing to atrophy, metaplasia, and gastric cancer. The overexpression of Cathepsin X/Z (Ctsz) in H. pylori-infected mucosa and gastric cancer is mediated predominantly by an augmented migration of ctsz(-/-)positive macrophages and the up-regulation of Ctsz in tumor epithelium. To explore the Ctsz-function in the context of chronic inflammation and the development of preneoplastic lesions, we used Ctsz-deficient mice in a H. pylori gastritis model. Ctsz (-/-) and wild-type (wt) mice were infected with H. pylori strain SS1. The mice were sacrificed at 24, 36, and 50 weeks post infection (wpi). The stomach was removed, and gastric strips were snap-frozen or embedded and stained with H&E. Tissue sections were scored for epithelial lesions and inflammation. Ki-67 and F4/80 immunostaining were used to measure epithelial cell proliferation and macrophage infiltration, respectively. The upregulation of compensating cathepsins and cytokines were confirmed by Western blotting and quantitative RT-PCR. SS1-infected wt and ctsz (-/-) mice showed strong inflammation, foveolar hyperplasia, atrophy, and cystically-dilated glands. However, at 50 wpi, ctsz (-/-) mice developed significantly more severe spasmolytic polypeptide-expressing metaplasia (SPEM), showed enhanced epithelial proliferation, and higher levels of infiltrating macrophages. Induction of cytokines was higher and significantly prolonged in ctsz (-/-) mice compared to wt. Ctsz deficiency supports H. pylori-dependent development of chronic gastritis up to metaplasia, indicating a protective, but not proteolytic, function of Ctsz in inflammatory gastric disease.Sabine KruegerAnja BernhardtThomas KalinskiMartin BaldenspergerMichael ZehAnne TellerDaniela AdolfThomas ReinheckelAlbert RoessnerDoerthe KuesterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e70242 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sabine Krueger Anja Bernhardt Thomas Kalinski Martin Baldensperger Michael Zeh Anne Teller Daniela Adolf Thomas Reinheckel Albert Roessner Doerthe Kuester Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
description	Helicobacter pylori are responsible for the induction of chronic gastric inflammation progressing to atrophy, metaplasia, and gastric cancer. The overexpression of Cathepsin X/Z (Ctsz) in H. pylori-infected mucosa and gastric cancer is mediated predominantly by an augmented migration of ctsz(-/-)positive macrophages and the up-regulation of Ctsz in tumor epithelium. To explore the Ctsz-function in the context of chronic inflammation and the development of preneoplastic lesions, we used Ctsz-deficient mice in a H. pylori gastritis model. Ctsz (-/-) and wild-type (wt) mice were infected with H. pylori strain SS1. The mice were sacrificed at 24, 36, and 50 weeks post infection (wpi). The stomach was removed, and gastric strips were snap-frozen or embedded and stained with H&E. Tissue sections were scored for epithelial lesions and inflammation. Ki-67 and F4/80 immunostaining were used to measure epithelial cell proliferation and macrophage infiltration, respectively. The upregulation of compensating cathepsins and cytokines were confirmed by Western blotting and quantitative RT-PCR. SS1-infected wt and ctsz (-/-) mice showed strong inflammation, foveolar hyperplasia, atrophy, and cystically-dilated glands. However, at 50 wpi, ctsz (-/-) mice developed significantly more severe spasmolytic polypeptide-expressing metaplasia (SPEM), showed enhanced epithelial proliferation, and higher levels of infiltrating macrophages. Induction of cytokines was higher and significantly prolonged in ctsz (-/-) mice compared to wt. Ctsz deficiency supports H. pylori-dependent development of chronic gastritis up to metaplasia, indicating a protective, but not proteolytic, function of Ctsz in inflammatory gastric disease.
format	article
author	Sabine Krueger Anja Bernhardt Thomas Kalinski Martin Baldensperger Michael Zeh Anne Teller Daniela Adolf Thomas Reinheckel Albert Roessner Doerthe Kuester
author_facet	Sabine Krueger Anja Bernhardt Thomas Kalinski Martin Baldensperger Michael Zeh Anne Teller Daniela Adolf Thomas Reinheckel Albert Roessner Doerthe Kuester
author_sort	Sabine Krueger
title	Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
title_short	Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
title_full	Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
title_fullStr	Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
title_full_unstemmed	Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.
title_sort	induction of premalignant host responses by cathepsin x/z-deficiency in helicobacter pylori-infected mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/612aaf29cdcb401cb9bdc5d0d3f564a3
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Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.

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