Helicobacter pylori cagA+ Strains and Dissociation of Gastric Epithelial Cell Proliferation From Apoptosis

Peek, RM; Sf, Moss; Kt, Tham; Perez-Perez, Guillermo I.; Wang, Silu; Gg, Miller; Atherton, JC; Pr, Holt; Mj, Blaser

doi:10.1093/jnci/89.12.863

Cited by 311 publications

(232 citation statements)

References 26 publications

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“…When cocultured with epithelial cell lines, H. pylori are antiproliferative and proapoptotic (115, S111), although cag signaling is essentially pro-proliferative (through MAPK signaling and expression of the transcription factor AP-1) (116,117) and pro-and antiapoptotic (through NF-κB signaling) (70,118). Animal models and human studies suggest that the net effect of H. pylori colonization is pro-proliferative and proapoptotic (95,96,119,120, S87, S88). Pro-proliferative signaling increases cell replication and the chance of mutation, whereas apoptosis may be protective by inducing death of DNA-damaged cells.…”

Section: Figurementioning

confidence: 99%

Helicobacter pylori persistence: biology and disease

Blaser¹,

Atherton²

2004

J. Clin. Invest.

777

540

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Helicobacter pylori are bacteria that have coevolved with humans to be transmitted from person to person and to persistently colonize the stomach. Their population structure is a model for the ecology of the indigenous microbiota. A well-choreographed equilibrium between bacterial effectors and host responses permits microbial persistence and health of the host but confers risk of serious diseases, including peptic ulceration and gastric neoplasia.

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Section: Figurementioning

confidence: 99%

Helicobacter pylori persistence: biology and disease

Blaser¹,

Atherton²

2004

J. Clin. Invest.

777

540

View full text Add to dashboard Cite

show abstract

“…H. pylori has been seen to induce apoptosis in patients with gastroduodenal ulcer and gastritis (50)(51)(52)(53)(54)(55). Some authors have seen greater than five-fold increases in the number of apoptotic cells in patients with duodenal ulcer versus those observed following H. pylori eradication (56). In vitro studies have shown that apoptosis is induced in tumor cell lines incubated with H. pylori (57), as is a cell cycle arrest between phases G1 and S (58).…”

Section: A Link Between H Pylori Apoptosis and Cell Proliferationmentioning

confidence: 99%

Helicobacter pylori infection and gastric mucosal epithelial cell apoptosis

Olivares

Gisbert

2005

Rev. esp. enferm. dig.

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“…3,[6][7][8] Infiltrating macrophages, in particular, produce various cytokines and growth factors such as IL-1β that could attract more inflammatory cells and induces the proliferation of gastric epithelial cells. 9,10 A recent study demonstrated that IL-1β physiologically induced by HP infection enhanced gastric inflammation and the number of gastric tumors using Il1b-mull mice. 11 Moreover, host factors secreted from gastric epithelial cells, such as Sonic Hedgehog, could also be involved in the initiation of gastritis, acting as a macrophage chemoattractant during HP infection.…”

mentioning

confidence: 99%

Osteopontin depletion decreases inflammation and gastric epithelial proliferation during Helicobacter pylori infection in mice

Lee

Kim

et al. 2015

Laboratory Investigation

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Osteopontin (OPN) is a multifunctional protein that plays a role in many physiological and pathological processes, including inflammation and tumorigenesis. Here, we investigated the involvement of OPN in Helicobacter pylori (HP)-induced gastritis using OPN knockout (KO) mice and OPN knockdown (KD) cell lines. HP-infected OPN KO mice showed significantly reduced gastritis compared with wild-type (WT) mice with decreased infiltration of macrophages and a reduction in HP-induced upregulation of IL-1β, TNF-α, and IFN-γ. HP-exposed OPN KD gastric cancer cells and macrophage-like cells showed an attenuated induction of these cytokines. We also demonstrated a reduction in the migration of monocytic and macrophage-like cells toward conditioned media harvested from HP-exposed OPN KD gastric cancer cells as well as reduced migration ability of OPN KD cells itself. In addition, HP-infected OPN KO mice showed decreased epithelial cell proliferation compared with HP-infected WT mice, in association with a reduction in MAPK pathway activation. OPN KD gastric cancer cell lines also showed lower proliferative activity and reduced MAPK activation than shRNA control cells after HP co-culture or after IL-1β and TNF-α treatment. Taken together, these results indicate that OPN exerts a considerable influence on HP-induced gastritis by modulating the production of cytokines and contributing to macrophage infiltration. Moreover, OPN-mediated activation of the MAPK pathway in gastric epithelial cells might contribute to epithelial changes following HP infection. Helicobacter pylori (HP) is a Gram-negative bacterial pathogen that selectively colonizes the human stomach. 1,2 Approximately half of the world's population is infected with HP, and its infection is strongly associated with chronic gastritis, peptic ulcers, and gastric cancer. 1,2 HP-infected gastric mucosa progresses through stages of chronic gastritis, glandular atrophy, intestinal metaplasia, dysplasia, and gastric cancer. 3 HP produce a variety of virulence factors such as CagA and VacA that can affect host intracellular signaling pathways and play an important role in determining the outcome of HP infection. 3 However, they are not absolute determinants of clinical outcomes because most individuals remain asymptomatic after HP infection. 4 The variable outcomes of HP infection can be attributed to inflammatory responses governed by host factors as well as HP virulence factors. 5 Indeed, polymorphisms of host interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are reported to be associated with the risk of HP-associated gastric cancer development. 4 HP-induced chronic inflammation induces DNA alterations and imbalanced epithelial cell turnover, providing opportunities for mitotic error that could ultimately contribute to the development of gastric cancer. 3,[6][7][8] Infiltrating macrophages, in particular, produce various cytokines and growth factors such as IL-1β that could attract more inflammatory cells and induces the proliferation of gastric epithelial cells....

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Helicobacter pylori cagA+ Strains and Dissociation of Gastric Epithelial Cell Proliferation From Apoptosis

Abstract: Increased cell proliferation in the absence of a corresponding increase in apoptosis may explain the heightened risk for gastric carcinoma that is associated with infection by cagA+ vacA s1a strains of H. pylori.

Cited by 311 publications

References 26 publications

Helicobacter pylori persistence: biology and disease

Helicobacter pylori persistence: biology and disease

Helicobacter pylori infection and gastric mucosal epithelial cell apoptosis

Osteopontin depletion decreases inflammation and gastric epithelial proliferation during Helicobacter pylori infection in mice

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