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Helicobacter pylori-induced matrix metallopeptidase-10 promotes gastric bacterial colonization and gastritis.

ABSTRACT: The interaction between gastric epithelium and immune response plays key roles in H. pylori-associated pathology. We demonstrated a procolonization and proinflammation role of MMP-10 in H. pylori infection. MMP-10 is elevated in gastric mucosa and is produced by gastric epithelial cells synergistically induced by H. pylori and IL-22 via the ERK pathway. Human gastric MMP-10 was correlated with H. pylori colonization and the severity of gastritis, and mouse MMP-10 from non-BM-derived cells promoted bacteria colonization and inflammation. H. pylori colonization and inflammation were attenuated in IL-22^-/-, MMP-10^-/-, and IL-22^-/-MMP-10^-/- mice. MMP-10-associated inflammation is characterized by the influx of CD8⁺ T cells, whose migration is induced via MMP-10-CXCL16 axis by gastric epithelial cells. Under the influence of MMP-10, Reg3a, E-cadherin, and zonula occludens-1 proteins decrease, resulting in impaired host defense and increased H. pylori colonization. Our results suggest that MMP-10 facilitates H. pylori persistence and promotes gastritis.

SUBMITTER: Lv YP

PROVIDER: S-EPMC6447374 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Helicobacter pylori-induced matrix metallopeptidase-10 promotes gastric bacterial colonization and gastritis.

Lv Yi-Pin YP Cheng Ping P Zhang Jin-Yu JY Mao Fang-Yuan FY Teng Yong-Sheng YS Liu Yu-Gang YG Kong Hui H Wu Xiao-Long XL Hao Chuan-Jie CJ Han Bin B Ma Qiang Q Yang Shi-Ming SM Chen Weisan W Peng Liu-Sheng LS Wang Ting-Ting TT Zou Quan-Ming QM Zhuang Yuan Y

Science advances 20190403 4

The interaction between gastric epithelium and immune response plays key roles in H. pylori-associated pathology. We demonstrated a procolonization and proinflammation role of MMP-10 in H. pylori infection. MMP-10 is elevated in gastric mucosa and is produced by gastric epithelial cells synergistically induced by H. pylori and IL-22 via the ERK pathway. Human gastric MMP-10 was correlated with H. pylori colonization and the severity of gastritis, and mouse MMP-10 from ...[more]

PMID: 30949574

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Project description:Background and objectivesHelicobacter pylori (H. pylori) infection is the most common etiology of chronic gastric. H. pylori gastritis would gradually evolve into gastric atrophy, intestinal metaplasia, dysplasia and malignant lesions. Herein, this study aimed to investigate the potential impact of H. pylori colonization density and depth on the severity of histological parameters of gastritis.MethodsA prospective monocentric study was conducted from December 2019 to July 2022, enrolling patients with confirmed chronic H. pylori infection via histopathological evaluation. H. pylori colonization status was detected by immunohistochemical staining, pathological changes of gastric specimens were detected by hematoxylin eosin staining. Epidemiological, endoscopic and histopathological data were collected.ResultsA total of 1120 patients with a mean age of 45.8 years were included. Regardless of the previous history of H. pylori eradication treatment, significant correlations were observed between the density and depth of H. pylori colonization and the intensity of gastritis activity (all P < 0.05). Patients with the lowest level of H. pylori colonization density and depth exhibited the highest level of mild activity. In whole participants and anti-H. pylori treatment-naive participants, H. pylori colonization density and depth were markedly correlated with the severity of chronic gastritis and gastric atrophy (all P < 0.05). H. pylori colonization density (P = 0.001) and depth (P = 0.047) were significantly associated with ulcer formation in patients naive to any anti-H. pylori treatment. No significant associations were observed between the density and depth of H. pylori colonization and other histopathological findings including lymphadenia, lymphoid follicle formation and dysplasia.ConclusionsAs the density and depth of H. pylori colonization increased, so did the activity and severity of gastritis, along with an elevated risk of ulcer formation.

Dataset Information

Helicobacter pylori-induced matrix metallopeptidase-10 promotes gastric bacterial colonization and gastritis.

Publications

<i>Helicobacter pylori</i>-induced matrix metallopeptidase-10 promotes gastric bacterial colonization and gastritis.

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