ArticleJournal of immunology (Baltimore, Md. : 1950)2008
Molecular characterization of Helicobacter pylori VacA induction of IL-8 in U937 cells reveals a prominent role for p38MAPK in activating transcription factor-2, cAMP response element binding protein, and NF-kappaB activation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 87 citations in OpenAlex.
- Garvicin Q-producing Lactococcus garvieae LG3092: its role in mitigating dysbiosis and H. pylori-associated gastritis.NPJ biofilms and microbiomes · 2025Article
- Neuroprotective effects of dantrolene in neurodegenerative disease: Role of inhibition of pathological inflammation.Journal of anesthesia and translational medicine · 2024Article
- Helicobacter pylori infection and Parkinson's Disease: etiology, pathogenesis and levodopa bioavailability.Immunity & ageing : I & A · 2024Review
- From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?Reviews in endocrine & metabolic disorders · 2021Review
- Dantrolene repurposed to treat sepsis or septic shock and COVID-19 patients.European review for medical and pharmacological sciences · 2021Review
- Evodiamine InhibitsInternational journal of molecular sciences · 2021Article
- Fighting the Antibiotic Crisis: Flavonoids as Promising Antibacterial Drugs AgainstFrontiers in cellular and infection microbiology · 2021Review
- Anti-inflammatory and anti-oxidative effect of Korean propolis on Helicobacter pylori-induced gastric damage in vitro.Journal of microbiology (Seoul, Korea) · 2020Article
- Could dantrolene be explored as a repurposed drug to treat COVID-19 patients by restoring intracellular calcium homeostasis?European review for medical and pharmacological sciences · 2020Article
- SQSTM1/p62 Controls mtDNA Expression and Participates in Mitochondrial Energetic Adaption via MRPL12.iScience · 2020Article
- Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice.Frontiers in aging neuroscience · 2020Article
- Roles of Cyclic AMP Response Element Binding Activation in the ERK1/2 and p38 MAPK Signalling Pathway in Central Nervous System, Cardiovascular System, Osteoclast Differentiation and Mucin and Cytokine Production.International journal of molecular sciences · 2019Review
- Classical Swine Fever Virus Infection and Its NS4A Protein Expression Induce IL-8 Production through MAVS Signaling Pathway in Swine Umbilical Vein Endothelial Cells.Frontiers in microbiology · 2017Article
- Pleiotropic cytotoxicity of VacA toxin in host cells and its impact on immunotherapy.BioImpacts : BI · 2017Review
- The Effect of Probiotic Plus Prebiotic Supplementation on the Tolerance and Efficacy ofMiddle East journal of digestive diseases · 2016Article
- Use of VacA as a Vaccine Antigen.Toxins · 2016Review
- Review
- Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis.Biomedical journal · 2016Review
- Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease.Biomolecules · 2015Review
- Transcriptional mechanisms and protein kinase signaling mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells.American journal of physiology. Lung cellular and molecular physiology · 2015Article
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Authors and funding
13 authors at 10 institutions in 3 countries.
Funding
Abstract
Helicobacter pylori VacA induces multiple effects on susceptible cells, including vacuolation, mitochondrial damage, inhibition of cell growth, and enhanced cyclooxygenase-2 expression. To assess the ability of H. pylori to modulate the production of inflammatory mediators, we examined the mechanisms by which VacA enhanced IL-8 production by promonocytic U937 cells, which demonstrated the greatest VacA-induced IL-8 release of the cells tested. Inhibitors of p38 MAPK (SB203580), ERK1/2 (PD98059), IkappaBalpha ((E)-3-(4-methylphenylsulfonyl)-2-propenenitrile), Ca(2+) entry (SKF96365), and intracellular Ca(2+) channels (dantrolene) blocked VacA-induced IL-8 production. Furthermore, an intracellular Ca(2+) chelator (BAPTA-AM), which inhibited VacA-activated p38 MAPK, caused a dose-dependent reduction in VacA-induced IL-8 secretion by U937 cells, implying a role for intracellular Ca(2+) in mediating activation of MAPK and the canonical NF-kappaB pathway. VacA stimulated translocation of NF-kappaBp65 to the nucleus, consistent with enhancement of IL-8 expression by activation of the NF-kappaB pathway. In addition, small interfering RNA of activating transcription factor (ATF)-2 or CREB, which is a p38MAPK substrate and binds to the AP-1 site of the IL-8 promoter, inhibited VacA-induced IL-8 production. VacA activated an IL-8 promoter containing an NF-IL-6 site, but not a mutated AP-1 or NF-kappaB site, suggesting direct involvement of the ATF-2/CREB binding region or NF-kappaB-binding regions in VacA-induced IL-8 promoter activation. Thus, in U937 cells, VacA directly increases IL-8 production by activation of the p38 MAPK via intracellular Ca(2+) release, leading to activation of the transcription factors, ATF-2, CREB, and NF-kappaB.
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Registered trials
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