Effect of low oxygen concentration on activation of inflammation by Helicobacter pylori

Abass, Adiza; Okano, Tokuju; Boonyaleka, Kotchakorn; Kinoshita-Daitoku, Ryo; Shoji, Yasuhiro; Ashida, Hiroshi; Suzuki, Toshihiko

doi:10.1016/j.bbrc.2021.04.123

Cited by 12 publications

(4 citation statements)

References 20 publications

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“…A primary finding of our study was that after H. pylori infection, we verified that H. pylori can induce HIF-1α and activate the PI3K/AKT signaling pathway. This result is consistent with previous studies[ 41 , 42 ], and HIF-1α overexpression amplified the activation effect of H. pylori on the PI3K/AKT pathway, while the effect was reversed in cells with HIF-1α knockdown. These findings demonstrated that HIF-1α can accelerate GC progression via the PI3K/AKT pathway during H. pylori infection.…”

Section: Discussionsupporting

confidence: 93%

N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway

An,

Hu,

et al. 2024

World J Gastrointest Oncol

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BACKGROUND Helicobacter pylori (H. pylori ) colonizes the human gastric mucosa and is implicated in the development of gastric cancer (GC). The tumor microenvironment is characterized by hypoxia, where hypoxia-inducible factor-1α (HIF-1α) plays a key role as a transcription factor, but the mechanisms underlying H. pylori -induced HIF-1α expression and carcinogenesis remain unclear. AIM To explore the underlying mechanism of H. pylori -induced HIF-1α expression in promoting the malignant biological behavior of gastric epithelial cells (GES-1). METHODS The study was conducted with human GES-1 cells in vitro . Relative protein levels of methyltransferase-like protein 14 (METTL14), HIF-1α, main proteins of the PI3K/AKT pathway, epithelial-mesenchymal transition (EMT) biomarkers, and invasion indicators were detected by Western blot. Relative mRNA levels of METTL14 and HIF-1α were detected by quantitative reverse transcription-polymerase chain reaction. mRNA stability was evaluated using actinomycin D, and the interaction between METTL14 and HIF-1α was confirmed by immunofluorescence staining. Cell proliferation and migration were evaluated by cell counting kit-8 assay and wound healing assay, respectively. RESULTS H. pylori promoted HIF-1α expression and activated the PI3K/AKT pathway. Notably, METTL14 was downregulated in H. pylori -infected gastric mucosal epithelial cells and positively regulated HIF-1α expression. Functional experiments showed that the overexpression of HIF-1α or knockdown of METTL14 enhanced the activity of the PI3K/AKT pathway, thereby driving a series of malignant transformation, such as EMT and cell proliferation, migration, and invasion. By contrast, the knockdown of HIF-1α or overexpression of METTL14 had an opposite effect. CONCLUSION H. pylori- induced underexpression of METTL14 promotes the translation of HIF-1α and accelerates tumor progression by activating the PI3K/AKT pathway. These results provide novel insights into the carcinogenesis of GC.

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Section: Discussionsupporting

confidence: 93%

N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway

An,

Hu,

et al. 2024

World J Gastrointest Oncol

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“…However, since both in vivo and in vitro, hypoxia stimulates growth of P. gingivalis more than normoxia, we conducted further analysis of the effects of bacterial growth under hypoxia on inflammasome activation. We previously reported that HIF-1α inhibition suppresses the enhancement of inflammasome activation in macrophages under hypoxia and colonization of the stomach by Helicobacter pylori infection; however, the underlying molecular mechanisms remain unknown 27 . Furthermore, we found that the proteins secreted from P. gingivalis are responsible for enhancing the inflammasome activation in the infected macrophages.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia drives progression of multiple sclerosis by enhancing the inflammasome activation in macrophages with Porphyromonas gingivalis infection.

Okano,

Ashida,

Tsukasaki

et al. 2024

Preprint

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Porphyromonas gingivalis (P. gingivalis), a gram-negative anaerobic bacterium, is the most common cause of periodontitis. P. gingivalis secretes several virulence factors, such as gingipains, LPS, and OMVs, which potentially induce the release of inflammatory cytokines such as IL-1β, TNFα, and IL-6 through inflammasome activation and TLRs. Previous reports have suggested that the host inflammatory response to P. gingivalis infection induces the progression of autoimmune diseases, including multiple sclerosis. We demonstrated enhancement of NLRP3 inflammasome activation in macrophages by P. gingivalis infection under hypoxia with inducing ROS. We also found that HIF-1α regulated by TRIF triggered exacerbation of inflammasome activation by P. gingivalis under hypoxia. Moreover, HIF-1α deficiency in myeloid cells recovered the progression of neurological symptoms in a mouse model of multiple sclerosis with P. gingivalis infection, including IL-1β and IL-17 production in the spleen. In this study, we showed that hypoxia controls inflammasome activation induced by periodontitis-associated bacterial infection, resulting in the progression of autoimmune diseases.

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“…H. pylori infection induced the expression of hypoxia-inducible factor[ 23 ], which is required for hypoxic induction of TET1 and global increase of 5-hmC. The proliferation rate of H. pylori under aerobic conditions was 3-fold higher than under microaerophilic conditions, and the bacterial growth was more dependent on carbon dioxide than on oxygen[ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Increased 5-hydroxymethylcytosine is a favorable prognostic factor of Helicobacter pylori-negative gastric cancer patients

Fu¹,

Wu²,

Cao³

et al. 2022

WJGO

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BACKGROUND Most gastric cancer (GC) patients are diagnosed at middle or late stage because the symptoms in early stage are obscure, which causes higher mortality rates of GC. Helicobacter pylori ( H. pylori ) was identified as a class I carcinogen and leads to aberrant DNA methylation/hydroxymethylation. 5-hydroxymethylcytosine (5-hmC) plays complex roles in gene regulation of tumorigenesis and can be considered as an activating epigenetic mark of hydroxymethylation. AIM To explore the association between 5-hmC levels and the progression and prognosis of GC patients with or without H. pylori infection . METHODS A retrospective cohort study was conducted to estimate the predicted value of 5-hmC level in the progression and prognosis of GC patients with different H. pylori infection status. A total of 144 GC patients were recruited. RESULTS The levels of 5-hmC were significantly decreased in tumor tissues (0.076 ± 0.048) compared with the matched control tissues (0.110 ± 0.057, P = 0.001). A high level of 5-hmC was an independent significant favorable predictor of overall survival in GC patients (hazard ratio = 0.61, 95% confidence interval: 0.38-0.98, P = 0.040), the H. pylori -negative GC subgroup (hazard ratio = 0.30, 95% confidence interval: 0.13-0.68, P = 0.004) and the GC patients with TNM stage Ⅰ or Ⅱ (hazard ratio = 0.32, 95% confidence interval: 0.13-0.77, P = 0.011). CONCLUSION Increased 5-hmC is a favorable prognostic factor in GC, especially for H. pylori -negative subgroups.

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Effect of low oxygen concentration on activation of inflammation by Helicobacter pylori

Cited by 12 publications

References 20 publications

N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway

N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway

Hypoxia drives progression of multiple sclerosis by enhancing the inflammasome activation in macrophages with Porphyromonas gingivalis infection.

Increased 5-hydroxymethylcytosine is a favorable prognostic factor of Helicobacter pylori-negative gastric cancer patients

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