Targeting hypoxia-inducible factor-1 alpha suppresses Helicobacter pylori-induced gastric injury via attenuation of both cag-mediated microbial virulence and proinflammatory host responses
| Title: | 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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| Authors: | 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 |
| Source: | Gut Microbes, Vol 15, Iss 2 (2023) |
| Publisher Information: | Taylor & Francis Group, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Diseases of the digestive system. Gastroenterology |
| Subject Terms: | 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 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 19490976 1949-0984 1949-0976 |
| Relation: | https://doaj.org/toc/1949-0976; https://doaj.org/toc/1949-0984 |
| DOI: | 10.1080/19490976.2023.2263936 |
| Access URL: | https://doaj.org/article/5ca1554c76e54c8382886b3806ff21b3 |
| Accession Number: | edsdoj.5ca1554c76e54c8382886b3806ff21b3 |
| Database: | Directory of Open Access Journals |
| ISSN: | 19490976 19490984 |
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| DOI: | 10.1080/19490976.2023.2263936 |
| Published in: | Gut Microbes |
| Language: | English |