NF-κB activation by Helicobacter pylori requires Akt-mediated phosphorylation of p65

BackgroundThe inflammatory response in Helicobacter pylori-infected gastric tissue is mediated by cag pathogenicity island (PAI)-dependent activation of nuclear factor-κB (NF-κB). Phosphatidylinositol 3-kinase (PI3K)/Akt signaling is known to play a role in NF-κB activation, but little information is available on the relationship between H. pylori and PI3K/Akt signaling in gastric epithelial cells. We examined whether H. pylori activates Akt in gastric epithelial cells, the role of cag PAI in this process and the role of Akt in regulating H. pylori-induced NF-κB activation.ResultsPhosphorylated Akt was detected in epithelial cells of H. pylori-positive gastric tissues. Although Akt was activated in MKN45 and AGS cells by coculture with cag PAI-positive H. pylori strains, a cag PAI-negative mutant showed no activation of Akt. H. pylori also induced p65 phosphorylation. PI3K inhibitor suppressed H. pylori-induced p65 phosphorylation and NF-κB transactivation, as well as interleukin-8 expression. Furthermore, transfection with a dominant-negative Akt inhibited H. pylori-induced NF-κB transactivation. Transfection with small interference RNAs for p65 and Akt also inhibited H. pylori-induced interleukin-8 expression.ConclusionThe results suggest that cag PAI-positive H. pylori activates Akt in gastric epithelial cells and this may contribute to H. pylori-mediated NF-κB activation associated with mucosal inflammation and carcinogenesis.

• Publication year

  2009

• Venue

  BMC Microbiology

• Publication date

  2009-02-12

• Fields of study

  Not labeled

• Identifiers
  DOI 10.1186/1471-2180-9-36PMCID 2653507
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Activation of Abl by Helicobacter pylori: a novel kinase for CagA and crucial mediator of host cell scattering.

  2007cited by this paper
• Helicobacter exploits integrin for type IV secretion and kinase activation

  2007cited by this paper
• Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells

  2007cited by this paper
• Pathogenicity island-dependent effects of Helicobacter pylori on intracellular signal transduction in epithelial cells.

  2005cited by this paper
• Helicobacter pylori and gastric cancer: a new paradigm for inflammation-associated epithelial cancers.

  2005cited by this paper
• NF-kappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein.

  2005cited by this paper
• Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation

  2005cited by this paper
• NF-κB RelA Phosphorylation Regulates RelA Acetylation

  2005cited by this paper
• Shaping the nuclear action of NF-κB

  2004cited by this paper
• p53 Induces NF-κB Activation by an IκB Kinase-independent Mechanism Involving Phosphorylation of p65 by Ribosomal S6 Kinase 1*

  2004cited by this paper
• Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin‐8

  2003cited by this paper
• Helicobacter pylori virulence factors--one part of a big picture.

  2003cited by this paper
• Functional Analysis of the Helicobacter pylori cag Pathogenicity Island Reveals Both VirD4-CagA-Dependent and VirD4-CagA-Independent Mechanisms

  2002cited by this paper
• Missing pieces in the NF-kappaB puzzle.

  2002cited by this paper
• The Phosphatidylinositol 3-Kinase-Akt Pathway Limits Lipopolysaccharide Activation of Signaling Pathways and Expression of Inflammatory Mediators in Human Monocytic Cells*

  2002cited by this paper
• Akt Stimulates the Transactivation Potential of the RelA/p65 Subunit of NF-κB through Utilization of the IκB Kinase and Activation of the Mitogen-activated Protein Kinase p38*

  2001cited by this paper
• Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus

  2000cited by this paper
• Toll-like receptor 2–mediated NF-κB activation requires a Rac1-dependent pathway

  2000cited by this paper
• Constitutive Activation Of Nf- κ B In Primary Adult T-cell Leukemia Cells

  1999cited by this paper
• Analyses of the cag pathogenicity island of Helicobacter pylori

  1998cited by this paper
• Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45

  1997cited by this paper
• The complete genome sequence of the gastric pathogen Helicobacter pylori

  1997cited by this paper
• [Helicobacter pylori].

  1996cited by this paper
• cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors.

  1996cited by this paper
• Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach.

  1995cited by this paper
• Induction of interleukin-8 secretion from gastric epithelial cells by a cagA negative isogenic mutant of Helicobacter pylori.

  1995cited by this paper
• Synergistic transcriptional activation of the IL-8 gene by NF-kappa B p65 (RelA) and NF-IL-6.

  1994cited by this paper
• Mucosal IgA recognition of Helicobacter pylori 120 kDa protein, peptic ulceration, and gastric pathology.

  1991cited by this paper
• [Inflammation and cancer].

  1974cited by this paper

• DEC1 promotes progression of Helicobacter pylori‐positive gastric cancer by regulating Akt/NF‐κB pathway

  2022cites this paper
• Aspilia africana C. D. Adams inhibits the production of lipopolysaccharide-induced inflammatory mediators in murine macrophage RAW264.7 cells by suppressing the NF-κB and PI3K/Akt pathways

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  2016cites this paper
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  2015cites this paper
• Helicobacter pylori-induced gastric inflammation and gastric cancer.

  2014cites this paper
• In house reverse membrane hybridisation assay versus GenoType MTBDRplus and their performance to detect mutations in the genes rpoB, katG and inhA

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• N-(p-Coumaryol)-Tryptamine Suppresses the Activation of JNK/c-Jun Signaling Pathway in LPS-Challenged RAW264.7 Cells

  2014cites this paper
• Helicobacter pylori and interleukin-8 in gastric cancer.

  2013cites this paper
• Differentiation of virulence of Helicobacter pylori by matrix-assisted laser desorption/ionization mass spectrometry and multivariate analyses.

  2013cites this paper
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  2013cites this paper
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  2012cites this paper
• Interaction effects between genes involved in the AKT signaling pathway and phytoestrogens in gastric carcinogenesis: a nested case-control study from the Korean Multi-Center Cancer Cohort.

  2012cites this paper
• Helicobacter pylori‐Associated Regulation of Forkhead Transcription Factors FoxO1/3a in Human Gastric Cells

  2012cites this paper
• Retraction: NF-κB activation by Helicobacter pylori requires Akt-mediated phosphorylation of p65

  2011cites this paper
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  2010cites this paper
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