Chronic inflammation of the gastric mucosa, often caused by autoimmune gastritis and/or infection with Helicobacter pylori, can lead to atrophy of acid-secreting parietal cells with metaplasia of remaining cells. The histological pattern marks a critical step in the progression from chronic gastritis to gastric cancer, yet underlying mechanism(s) of inflammation-induced cell death of gastric epithelial cells are poorly understood. We investigated direct effects of a type 1 cytokine associated with autoimmunity and infection, interferon-γ (IFN-γ), on gastric epithelial cells. IFN-γ was applied to three-dimensional organoid cultures of gastric epithelial cells derived from gastric corpus gland (gastroids) of control and IFN-γ receptor-deficient mice. Gastroids were also treated with supernatants from activated immune cells isolated from a mouse model of autoimmune-mediated atrophic gastritis (TxA23) with and without IFN-γ expression. Finally, histopathological analysis of atrophy and metaplasia severity was performed in TxA23 mice and compared to TxA23 × Ifng mice. Gastric epithelial cells in gastroid cultures expressed IFN-γ receptor in the basolateral membrane, and gastroids died when treated with IFN-γ in an IFN-γ receptor-dependent manner. Supernatants from immune cells containing high levels of IFN-γ were highly toxic to gastroids, and toxicity was tempered when IFN-γ was either neutralized using a monoclonal antibody or when supernatants from Ifng mouse immune cells were used. Finally, TxA23 × Ifng mice showed near-complete abrogation of pre-cancerous histopathological atrophy and metaplasia versus IFN-γ-sufficient controls. We identify IFN-γ as a critical promoter of parietal cell atrophy with metaplasia during the progression of gastritis to gastric atrophy and metaplasia. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5214 | DOI Listing |
Am J Transl Res
December 2024
Department of Gastroenterology, Shandong Provincial Hospital, Shandong University Jinan 250014, Shandong, China.
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Anticancer Agents Med Chem
January 2025
Laboratory Animal Center, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, P.R. China.
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J Gastrointest Oncol
December 2024
Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.
Gastric cancer (GC) ranks among the top five most diagnosed cancers globally, with particularly high incidence and mortality rates observed in Asian regions. Despite certain advancements achieved through early screening and treatment strategies in many countries, GC continues to pose a significant public health challenge. Approximately 20% of patients infected with develop precancerous lesions, among which metaplasia is the most critical.
View Article and Find Full Text PDFJ Gastrointest Oncol
December 2024
Department of Gastroenterological Surgery and Hernia Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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