Helicobacter pylori-induced adrenomedullin modulates IFN-γ-producing T-cell responses and contributes to gastritis
| العنوان: | Helicobacter pylori-induced adrenomedullin modulates IFN-γ-producing T-cell responses and contributes to gastritis |
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| المؤلفون: | Nan You, Yuan Zhuang, Ping Cheng, Jin-yu Zhang, Zhuo Zhao, Yi-pin Lv, Yu-gang Liu, Han Chen, Fang-yuan Mao, Weisan Chen, Hui Kong, Quanming Zou, Gang Guo, Yong-sheng Teng |
| المصدر: | Cell Death and Disease, Vol 11, Iss 3, Pp 1-15 (2020) Cell Death & Disease |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, T-Lymphocytes, Vasodilator Agents, T cell, Immunology, Inflammation, Article, Adrenomedullin, Interferon-gamma, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Gastric mucosa, medicine, Animals, Humans, lcsh:QH573-671, STAT3, Protein kinase B, Helicobacter pylori, biology, Chemistry, lcsh:Cytology, Chronic inflammation, Cell Biology, biology.organism_classification, 030104 developmental biology, medicine.anatomical_structure, Gastritis, biology.protein, Cancer research, medicine.symptom, Infection, 030215 immunology |
| الوصف: | Adrenomedullin (ADM) is a multifunctional peptide that is expressed by many surface epithelial cells, but its relevance to Helicobacter pylori (H. pylori)-induced gastritis is unknown. Here, we found that gastric ADM expression was elevated in gastric mucosa of H. pylori-infected patients and mice. In H. pylori-infected human gastric mucosa, ADM expression was positively correlated with the degree of gastritis; accordingly, blockade of ADM resulted in decreased inflammation within the gastric mucosa of H. pylori-infected mice. During H. pylori infection, ADM production was promoted via PI3K–AKT signaling pathway activation by gastric epithelial cells in a cagA-dependent manner, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterized by the increased IFN-γ-producing T cells, whose differentiation was induced via the phosphorylation of AKT and STAT3 by ADM derived from gastric epithelial cells. ADM also induced macrophages to produce IL-12, which promoted the IFN-γ-producing T-cell responses, thereby contributing to the development of H. pylori-associated gastritis. Accordingly, blockade of IFN-γ or knockout of IFN-γ decreased inflammation within the gastric mucosa of H. pylori-infected mice. This study identifies a novel regulatory network involving H. pylori, gastric epithelial cells, ADM, macrophages, T cells, and IFN-γ, which collectively exert a pro-inflammatory effect within the gastric microenvironment. |
| اللغة: | English |
| تدمد: | 2041-4889 |
| DOI: | 10.1038/s41419-020-2391-6 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::188ae00a125af8a8c211b2a931320c26 http://link.springer.com/article/10.1038/s41419-020-2391-6 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....188ae00a125af8a8c211b2a931320c26 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
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| DOI: | 10.1038/s41419-020-2391-6 |