Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2016; 22(33): 7536-7558
Published online Sep 7, 2016. doi: 10.3748/wjg.v22.i33.7536
Impact of Helicobacter pylori on the healing process of the gastric barrier
Eliza Mnich, Magdalena Kowalewicz-Kulbat, Paulina Sicińska, Krzysztof Hinc, Michał Obuchowski, Adrian Gajewski, Anthony P Moran, Magdalena Chmiela
Eliza Mnich, Magdalena Kowalewicz-Kulbat, Adrian Gajewski, Magdalena Chmiela, Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Łódź, 90-237 Łódź, Poland
Paulina Sicińska, Department of Biophysics of Environment Pollution, Faculty of Biology and Environmental Protection, University of Łódź, 90-237 Łódź, Poland
Krzysztof Hinc, Michał Obuchowski, Laboratory of Molecular Bacteriology, Intercollegiate Faculty of Biotechnology UG-MUG, Medical University of Gdańsk, 80-210 Gdańsk, Poland
Anthony P Moran, Department of Microbiology, Laboratory of Molecular Biochemistry, University College, 9014 Galway, Ireland
Author contributions: Mnich E, Chmiela M substantially contributed to the conception and design of the research, performed analysis and data interpretation; Mnich E participated in all experiments; Kowalewicz-Kulbat M and Sicińska P performed the cell cycle and apoptosis assay; Gajewski A participated in DAPI staining; Hinc K, Obuchowski M and Moran AP provided essential reagents: subunit A of urease, H. pylori LPS; Mnich E and Kowalewicz-Kulbat M performed statistical analysis; all authors drafted the article and made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Supported by National Science Centre of Poland, No. DEC-2013/09/N/NZ6/00805 and No. DEC-2015/17/N/NZ6/03490.
Conflict-of-interest statement: The authors have no competing interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Magdalena Chmiela, Professor, PhD, Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland.
Telephone: +48-42-6354186 Fax: +48-42-6655818
Received: May 7, 2016
Peer-review started: May 8, 2016
First decision: May 20, 2016
Revised: June 29, 2016
Accepted: July 20, 2016
Article in press: July 20, 2016
Published online: September 7, 2016

To determine the impact of selected well defined Helicobacter pylori (H. pylori) antigens on gastric barrier cell turnover.


In this study, using two cellular models of gastric epithelial cells and fibroblasts, we have focused on exploring the effects of well defined H. pylori soluble components such as glycine acid extract antigenic complex (GE), subunit A of urease (UreA), cytotoxin associated gene A protein (CagA) and lipopolysaccharide (LPS) on cell turnover by comparing the wound healing capacity of the cells in terms of their proliferative and metabolic activity as well as cell cycle distribution. Toxic effects of H. pylori components have been assessed in an association with damage to cell nuclei and inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation.


We showed that H. pylori GE, CagA and UreA promoted regeneration of epithelial cells and fibroblasts, which is necessary for effective tissue healing. However, in vivo increased proliferative activity of these cells may constitute an increased risk of gastric neoplasia. In contrast, H. pylori LPS showed a dose-dependent influence on the process of wound healing. At a low concentration (1 ng/mL) H. pylori LPS accelerated of healing epithelial cells, which was linked to significantly enhanced cell proliferation and MTT reduction as well as lack of alterations in cell cycle and downregulation of epidermal growth factor (EGF) production as well as cell nuclei destruction. By comparison, H. pylori LPS at a high concentration (25 ng/mL) inhibited the process of wound repair, which was related to diminished proliferative activity of the cells, cell cycle arrest, destruction of cell nuclei and downregulation of the EGF/STAT3 signalling pathway.


In vivo H. pylori LPS driven effects might lead to the maintenance of chronic inflammatory response and pathological disorders on the level of the gastric mucosal barrier.

Keywords: Helicobacter pylori, Wound healing, Gastric barrier dysfunction

Core tip: This manuscript focused on the impact of Helicobacter pylori (H. pylori) antigens to the gastric mucosal barrier. We evaluated the effects of H. pylori antigens using in vitro two cellular models of gastric epithelial cells and fibroblasts, which had been independently exposed to H. pylori components. In this study, we showed different effects of subunit A of urease, cytotoxin associated gene A protein, lipopolysaccharide (LPS) as well as compounds included in a glycine acid extract on the regenerative activity of gastric epithelial cells and fibroblasts. Our results indicate deleterious, dose dependent influence of H. pylori LPS on this process.