دورية أكاديمية
Targeting hypoxia-inducible factor-1 alpha suppresses Helicobacter pylori-induced gastric injury via attenuation of both cag-mediated microbial virulence and proinflammatory host responses
العنوان: | Targeting hypoxia-inducible factor-1 alpha suppresses Helicobacter pylori-induced gastric injury via attenuation of both cag-mediated microbial virulence and proinflammatory host responses |
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المؤلفون: | Jennifer M. Noto, M. Blanca Piazuelo, Judith Romero-Gallo, Alberto G. Delgado, Giovanni Suarez, Konstantina Akritidou, Miguel Girod Hoffman, Juan Carlos Roa, Cormac T. Taylor, Richard M. Peek |
المصدر: | Gut Microbes, Vol 15, Iss 2 (2023) |
بيانات النشر: | Taylor & Francis Group, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Diseases of the digestive system. Gastroenterology |
مصطلحات موضوعية: | Helicobacter pylori, gastric inflammation, gastric cancer, hypoxia-inducible factor-1 alpha (HIF-1α), dimethyloxalylglycine (DMOG), prolyl hydroxylase (PHD), Diseases of the digestive system. Gastroenterology, RC799-869 |
الوصف: | ABSTRACTHelicobacter pylori-induced inflammation is the strongest known risk factor for gastric adenocarcinoma. Hypoxia-inducible factor-1 (HIF-1α) is a key transcriptional regulator of immunity and carcinogenesis. To examine the role of this mediator within the context of H. pylori-induced injury, we first demonstrated that HIF-1α levels were significantly increased in parallel with the severity of gastric lesions in humans. In interventional studies targeting HIF-1α, H. pylori-infected mice were treated ± dimethyloxalylglycine (DMOG), a prolyl hydroxylase inhibitor that stabilizes HIF-1α. H. pylori significantly increased proinflammatory chemokines/cytokines and inflammation in vehicle-treated mice; however, this was significantly attenuated in DMOG-treated mice. DMOG treatment also significantly decreased function of the H. pylori type IV secretion system (T4SS) in vivo and significantly reduced T4SS-mediated NF-κB activation and IL-8 induction in vitro. These results suggest that prolyl hydroxylase inhibition protects against H. pylori-mediated pathologic responses, and is mediated, in part, via attenuation of H. pylori cag-mediated virulence and suppression of host proinflammatory responses. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 19490976 1949-0984 1949-0976 |
العلاقة: | https://doaj.org/toc/1949-0976Test; https://doaj.org/toc/1949-0984Test |
DOI: | 10.1080/19490976.2023.2263936 |
الوصول الحر: | https://doaj.org/article/5ca1554c76e54c8382886b3806ff21b3Test |
رقم الانضمام: | edsdoj.5ca1554c76e54c8382886b3806ff21b3 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19490976 19490984 |
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DOI: | 10.1080/19490976.2023.2263936 |