The contribution of toll-like receptor 2 on Helicobacter pylori activation of the nuclear factor-kappa B signaling pathway in gastric epithelial cells

Li, Shu; Cao, Mei; Song, Lingyun; Qi, Panpan; Chen, Chong; Wang, Xuege; Li, Ningzhe; Peng, Jingshan; Wu, Daoyan; Hu, Guoku; Zhao, Jian

doi:10.1016/j.micpath.2016.06.028

Cited by 17 publications

(8 citation statements)

References 35 publications

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“…The schematic shown in Figure 5B summarizes our current thinking, although some questions related to the induction of HIF-1α through signaling by TLR2 remain to be addressed in future studies. First, it still remains unclear which of the urease subunits is responsible for the activation of TLR2; second, it remains to be determined whether the increase in HIF-1α is due to the stabilization of the protein or due to an increase in the levels of transcription, possibly via NF-kB, since H. pylori reportedly activates NF-κB through TLR2 [45]. As described by our laboratory, H. pylori induces HIF-1α activity as a transcription factor via a PI3K-dependent pathway to produce G0/G1 cell cycle arrest in epithelial gastric cells [30].…”

Section: Discussionmentioning

confidence: 99%

The Helicobacter pylori Urease Virulence Factor Is Required for the Induction of Hypoxia-Induced Factor-1α in Gastric Cells

Valenzuela-Valderrama

Cerda-Opazo

Backert

et al. 2019

Cancers

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Chronic Helicobacter pylori infection increases the risk of gastric cancer and induction of hypoxia-induced factor (HIF), which is frequently associated with the development and progression of several types of cancer. We recently showed that H. pylori activation of the PI3K-AKT-mTOR pathway in gastric cells increased HIF-1α expression. Here, we identified the H. pylori virulence factor responsible for HIF-1α induction. A mutant of the H. pylori 84-183 strain was identified with reduced ability to induce HIF-1α. Coomassie blue staining of extracts from these bacteria separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed poor expression of urease subunits that correlated with reduced urease activity. This finding was confirmed in the 26695 strain, where urease mutants were unable to induce HIF-1α expression. Of note, HIF-1α induction was also observed in the presence of the urease inhibitor acetohydroxamic acid at concentrations (of 20 mM) that abrogated urease activity in bacterial culture supernatants, suggesting that enzymatic activity of the urease is not required for HIF-1α induction. Finally, the pre-incubation of the human gastric adenocarcinoma cell line AGS with blocking antibodies against Toll-like receptor-2 (TLR2), but not TLR4, prevented HIF-1α induction. In summary, these results reveal a hitherto unexpected role for the urease protein in HIF-1α induction via TLR2 activation following H. pylori infection of gastric cells.

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Section: Discussionmentioning

confidence: 99%

The Helicobacter pylori Urease Virulence Factor Is Required for the Induction of Hypoxia-Induced Factor-1α in Gastric Cells

Valenzuela-Valderrama

Cerda-Opazo

Backert

et al. 2019

Cancers

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“…However, the TLR2 expression on the surface of intestinal and gastric epithelial cells is increased during H. pylori infection and plays important roles in the regulating of gastrointestinal immune responses [42]. The TLR2 and TLR4 expression by the gastric epithelial cells from H. pylori-infected patients with chronic gastritis was higher than H. pylori-uninfected subjects.…”

Section: H Pylori Induces Tlr2-related Signaling In Gastrointestinalmentioning

confidence: 96%

“…Furthermore, H. pylori-induced COX-2 expression is prevented in TLR2-deficient cells, but not in TLR4-reduced cells, suggesting that H. pylori stimulates COX-2 production through a TLR2-related manner [42,51]. Figure 2 and Figure 3 illustrate the TLR2-related responses during H. pylori infection.…”

Section: Accepted Manuscriptmentioning

confidence: 97%

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Toll-like receptor 2: An important immunomodulatory molecule during Helicobacter pylori infection

et al. 2017

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“…Subversion of TLRs is dependent on recognition by H. pylori which helps the bacterium to survive in the strongly immune cell-rich gastric microniche[119-122]. TLR4-mediated inflammatory response to LPS in H. pylori is largely different to other organisms (almost 1000-fold less reactogenic than other Gram negative bacteria)[123-129]. Indeed, co-evolution with humans has resulted in a reduction in immunogenic ligands[130].…”

Section: Subversion Of Pattern Recognitionmentioning

confidence: 99%

Strategies used byhelicobacter pylorito establish persistent infection

Abadi

2017

WJG

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Helicobacter pylori (H. pylori) is a Gram-negative and motile bacterium that colonizes the hostile microniche of the human stomach, then persists for the host’s entire life, if not effectively treated. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, it is no exaggeration to conclude that smart strategies are contributing to adaptation of the bacterium to its permanent host. Thirty-four years after the discovery of this bacterium, there are still many unanswered questions. For example, which strategies help the bacterium to survive in this inhospitable microniche? This question is slightly easier to answer if we presume the same clinical concept for both persistent infection and disease. Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of diseases such as gastric cancer in patients infected with this bacterium. A well-defined and long-term equilibrium between the human host and H. pylori allows bacterial persistence in the gastric microniche; although this coexistence leads to a high risk of severe diseases such as gastric cancer. To escape the bactericidal activity of stomach acid, H. pylori secretes large amounts of surface-associated and cytosolic urease. The potential to avoid acidic conditions and immune evasion are discussed in order to explain the persistence of H. pylori colonization in the gastric mucosa, and data on bacterial genetic diversity are included. Information on the mechanisms related to H. pylori persistence can also provide the direction for future research concerning effective therapy and management of gastroduodenal disorders. The topics presented in the current review are important for elucidating the strategies used by H. pylori to help the bacterium persist in relation to the immune system and the many unfavorable features of living in the gastric microniche.

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The contribution of toll-like receptor 2 on Helicobacter pylori activation of the nuclear factor-kappa B signaling pathway in gastric epithelial cells

Cited by 17 publications

References 35 publications

The Helicobacter pylori Urease Virulence Factor Is Required for the Induction of Hypoxia-Induced Factor-1α in Gastric Cells

The Helicobacter pylori Urease Virulence Factor Is Required for the Induction of Hypoxia-Induced Factor-1α in Gastric Cells

Toll-like receptor 2: An important immunomodulatory molecule during Helicobacter pylori infection

Strategies used byhelicobacter pylorito establish persistent infection

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