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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
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.
Eliza
E
Mnich
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.
Magdalena
M
Kowalewicz-Kulbat
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
P
Sicińska
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.
Krzysztof
K
Hinc
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.
Michał
M
Obuchowski
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.
Adrian
A
Gajewski
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.
Anthony P
AP
Moran
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.
Magdalena
M
Chmiela
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology*; D005998:Glycine / Q000378:metabolism; D006168:Guinea Pigs; D016481:Helicobacter Infections / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D016480:Helicobacter pylori; D006801:Humans; D008070:Lipopolysaccharides; D015398:Signal Transduction; D013270:Stomach / Q000382:microbiology / Q000473:pathology*; D013274:Stomach Neoplasms / Q000382:microbiology / Q000473:pathology*; D014510:Urease / Q000378:metabolism; D014945:Wound Healing
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008070:Lipopolysaccharides; C080866:cagA protein, Helicobacter pylori; D014510:Urease; D005998:Glycine
Gastric barrier dysfunction; Helicobacter pylori; Wound healing
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