Targeting hypoxia-inducible factor-1 alpha suppresses <i>Helicobacter pylori</i>-induced gastric injury via attenuation of both <i>cag</i>-mediated microbial virulence and proinflammatory host responses

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dc.contributor.authorNoto, Jennifer M.
dc.contributor.authorPiazuelo, M. Blanca
dc.contributor.authorRomero-Gallo, Judith
dc.contributor.authorDelgado, Alberto G.
dc.contributor.authorSuarez, Giovanni
dc.contributor.authorAkritidou, Konstantina
dc.contributor.authorHoffman, Miguel Girod
dc.contributor.authorRoa, Juan Carlos
dc.contributor.authorTaylor, Cormac T.
dc.contributor.authorPeek, Richard M., Jr.
dc.date.accessioned2025-01-20T17:28:02Z
dc.date.available2025-01-20T17:28:02Z
dc.date.issued2023
dc.description.abstractHelicobacter pylori-induced inflammation is the strongest known risk factor for gastric adenocarcinoma. Hypoxia-inducible factor-1 (HIF-1 alpha) 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-1 alpha levels were significantly increased in parallel with the severity of gastric lesions in humans. In interventional studies targeting HIF-1 alpha, H. pylori-infected mice were treated +/- dimethyloxalylglycine (DMOG), a prolyl hydroxylase inhibitor that stabilizes HIF-1 alpha. 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-kappa B 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.
dc.fuente.origenWOS
dc.identifier.doi10.1080/19490976.2023.2263936
dc.identifier.eissn1949-0984
dc.identifier.issn1949-0976
dc.identifier.urihttps://doi.org/10.1080/19490976.2023.2263936
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/91580
dc.identifier.wosidWOS:001083972300001
dc.issue.numero2
dc.language.isoen
dc.revistaGut microbes
dc.rightsacceso restringido
dc.subjectHelicobacter pylori
dc.subjectgastric inflammation
dc.subjectgastric cancer
dc.subjecthypoxia-inducible factor-1 alpha (HIF-1 alpha)
dc.subjectdimethyloxalylglycine (DMOG)
dc.subjectprolyl hydroxylase (PHD)
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleTargeting hypoxia-inducible factor-1 alpha suppresses <i>Helicobacter pylori</i>-induced gastric injury via attenuation of both <i>cag</i>-mediated microbial virulence and proinflammatory host responses
dc.typeartículo
dc.volumen15
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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