Interleukin-17A Promotes Parietal Cell Atrophy by Inducing ApoptosisSummary
Background & Aims: Atrophic gastritis caused by chronic inflammation in the gastric mucosa leads to the loss of gastric glandular cells, including acid-secreting parietal cells. Parietal cell atrophy in a setting of chronic inflammation induces spasmolytic polypeptide expressing metaplasia, a cr...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X17301911 |
| _version_ | 1830354984856715264 |
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| author | Kevin A. Bockerstett Luciana H. Osaki Christine P. Petersen Catherine W. Cai Chun Fung Wong Thanh-Long M. Nguyen Eric L. Ford Daniel F. Hoft Jason C. Mills James R. Goldenring Richard J. DiPaolo |
| author_facet | Kevin A. Bockerstett Luciana H. Osaki Christine P. Petersen Catherine W. Cai Chun Fung Wong Thanh-Long M. Nguyen Eric L. Ford Daniel F. Hoft Jason C. Mills James R. Goldenring Richard J. DiPaolo |
| author_sort | Kevin A. Bockerstett |
| collection | DOAJ |
| description | Background & Aims: Atrophic gastritis caused by chronic inflammation in the gastric mucosa leads to the loss of gastric glandular cells, including acid-secreting parietal cells. Parietal cell atrophy in a setting of chronic inflammation induces spasmolytic polypeptide expressing metaplasia, a critical step in gastric carcinogenesis. However, the mechanisms by which inflammation causes parietal cell atrophy and spasmolytic polypeptide expressing metaplasia are not well defined. We investigated the role of interleukin-17A (IL-17A) in causing parietal cell atrophy. Methods: A mouse model of autoimmune atrophic gastritis was used to examine IL-17A production during early and late stages of disease. Organoids derived from corpus glands were used to determine the direct effects of IL-17A on gastric epithelial cells. Immunofluorescent staining was used to examine IL-17A receptors and the direct effect of signaling on parietal cells. Mice were infected with an IL-17A-producing adenovirus to determine the effects of IL-17A on parietal cells in vivo. Finally, IL-17A neutralizing antibodies were administered to mice with active atrophic gastritis to evaluate the effects on parietal cell atrophy and metaplasia. Results: Increased IL-17A correlated with disease severity in mice with chronic atrophic gastritis. IL-17A caused caspase-dependent gastric organoid degeneration, which could not be rescued with a necroptosis inhibitor. Parietal cells expressed IL-17A receptors and IL-17A treatment induced apoptosis in parietal cells. Overexpressing IL-17A in vivo induced caspase-3 activation and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling staining in parietal cells. Finally, IL-17A neutralizing antibody decreased parietal cell atrophy and metaplasia in mice with chronic atrophic gastritis. Conclusions: These data identify IL-17A as a cytokine that promotes parietal cell apoptosis during atrophic gastritis, a precursor lesion for gastric cancer. Keywords: IL-17A, Atrophy, Metaplasia, Apoptosis |
| first_indexed | 2024-12-20T01:40:05Z |
| format | Article |
| id | doaj.art-03d558bdbb2845c2af977f371340bbfc |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-20T01:40:05Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-03d558bdbb2845c2af977f371340bbfc2022-12-21T19:57:54ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2018-01-0154678690.e1Interleukin-17A Promotes Parietal Cell Atrophy by Inducing ApoptosisSummaryKevin A. Bockerstett0Luciana H. Osaki1Christine P. Petersen2Catherine W. Cai3Chun Fung Wong4Thanh-Long M. Nguyen5Eric L. Ford6Daniel F. Hoft7Jason C. Mills8James R. Goldenring9Richard J. DiPaolo10Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, MissouriDivision of Gastroenterology, Departments of Medicine, Pathology and Immunology, Developmental Biology, Washington University School of Medicine, St Louis, MissouriNashville VA Medical Center and Departments of Surgery and Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TennesseeDepartment of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, MissouriDepartment of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, MissouriDepartment of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, MissouriDepartment of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, MissouriDepartment of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, MissouriDivision of Gastroenterology, Departments of Medicine, Pathology and Immunology, Developmental Biology, Washington University School of Medicine, St Louis, MissouriNashville VA Medical Center and Departments of Surgery and Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TennesseeDepartment of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, Missouri; Correspondence Address correspondence to: Richard DiPaolo, PhD, Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, DRC 707, 1100 South Grand Boulevard, St. Louis, Missouri 63104. fax: (314) 977-8717.Background & Aims: Atrophic gastritis caused by chronic inflammation in the gastric mucosa leads to the loss of gastric glandular cells, including acid-secreting parietal cells. Parietal cell atrophy in a setting of chronic inflammation induces spasmolytic polypeptide expressing metaplasia, a critical step in gastric carcinogenesis. However, the mechanisms by which inflammation causes parietal cell atrophy and spasmolytic polypeptide expressing metaplasia are not well defined. We investigated the role of interleukin-17A (IL-17A) in causing parietal cell atrophy. Methods: A mouse model of autoimmune atrophic gastritis was used to examine IL-17A production during early and late stages of disease. Organoids derived from corpus glands were used to determine the direct effects of IL-17A on gastric epithelial cells. Immunofluorescent staining was used to examine IL-17A receptors and the direct effect of signaling on parietal cells. Mice were infected with an IL-17A-producing adenovirus to determine the effects of IL-17A on parietal cells in vivo. Finally, IL-17A neutralizing antibodies were administered to mice with active atrophic gastritis to evaluate the effects on parietal cell atrophy and metaplasia. Results: Increased IL-17A correlated with disease severity in mice with chronic atrophic gastritis. IL-17A caused caspase-dependent gastric organoid degeneration, which could not be rescued with a necroptosis inhibitor. Parietal cells expressed IL-17A receptors and IL-17A treatment induced apoptosis in parietal cells. Overexpressing IL-17A in vivo induced caspase-3 activation and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling staining in parietal cells. Finally, IL-17A neutralizing antibody decreased parietal cell atrophy and metaplasia in mice with chronic atrophic gastritis. Conclusions: These data identify IL-17A as a cytokine that promotes parietal cell apoptosis during atrophic gastritis, a precursor lesion for gastric cancer. Keywords: IL-17A, Atrophy, Metaplasia, Apoptosishttp://www.sciencedirect.com/science/article/pii/S2352345X17301911 |
| spellingShingle | Kevin A. Bockerstett Luciana H. Osaki Christine P. Petersen Catherine W. Cai Chun Fung Wong Thanh-Long M. Nguyen Eric L. Ford Daniel F. Hoft Jason C. Mills James R. Goldenring Richard J. DiPaolo Interleukin-17A Promotes Parietal Cell Atrophy by Inducing ApoptosisSummary Cellular and Molecular Gastroenterology and Hepatology |
| title | Interleukin-17A Promotes Parietal Cell Atrophy by Inducing ApoptosisSummary |
| title_full | Interleukin-17A Promotes Parietal Cell Atrophy by Inducing ApoptosisSummary |
| title_fullStr | Interleukin-17A Promotes Parietal Cell Atrophy by Inducing ApoptosisSummary |
| title_full_unstemmed | Interleukin-17A Promotes Parietal Cell Atrophy by Inducing ApoptosisSummary |
| title_short | Interleukin-17A Promotes Parietal Cell Atrophy by Inducing ApoptosisSummary |
| title_sort | interleukin 17a promotes parietal cell atrophy by inducing apoptosissummary |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X17301911 |
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