Helicobacter pylori increases proliferation of gastric epithelial cells.

Fan, Xue‐Gong; Kelleher, Dermot; Fan, X. J.; Xia, Hhx; Keeling, P. W. N.

doi:10.1136/gut.38.1.19

Cited by 132 publications

(88 citation statements)

References 17 publications

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“…Fan et al reported a similar increase of Ki-67-positive cells in H. pylori-associated gastritis in humans. 19 In the fundic mucosa the BrdU labeling indices increased slightly but significantly at 4 weeks after inoculation, although the inflammatory cell infiltration remained almost negligible in the corpus. One could speculate that the inflammation in the pyloric mucosa might influence the cell turnover in the fundus.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori-Induced Chronic Active Gastritis, Intestinal Metaplasia, and Gastric Ulcer in Mongolian Gerbils

Ikeno

Ota

Sugiyama

et al. 1999

The American Journal of Pathology

150

116

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Section: Discussionmentioning

confidence: 99%

Helicobacter pylori-Induced Chronic Active Gastritis, Intestinal Metaplasia, and Gastric Ulcer in Mongolian Gerbils

Ikeno

Ota

Sugiyama

et al. 1999

The American Journal of Pathology

150

116

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“…9,22,32,33 The gastric epithelial cell proliferation results from both the direct effects of HP pathogenic factor, such as CagA, 34 and the indirect effects of inflammatory environment enriched with cytokines, such as TNF-α and IL-1β, induced by HP infection 24,35 that could activate the MAPK cascades. As expected, HP-infected WT mice showed elevated gastric epithelial proliferation in association with enhanced MAPK pathway activation.…”

Section: Discussionmentioning

confidence: 99%

“…21,22 Based on the low degree of mucosal hyperplasia in OPN KO mice compared with WT mice after HP infection (Supplementary Figure S2), we performed IHC for Ki-67 on stomach tissues of HP-infected mice to investigate the impact Roles of osteopontin in H. pylori infection JW Park et al of the lack of OPN on gastric epithelial proliferation in response to HP infection. We found out that the number of Ki-67-positive gastric epithelial cells in HP-infected WT mice at 8 and 16 weeks after HP infection was significantly higher than that of uninfected WT mice (Figures 5a and b).…”

Section: Opn Deficiency Inhibits the Proliferation Of Gastricmentioning

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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“…H. pylori strains or rMIF was incubated with GECs for 24 h. Cells were lysed as described previously (32). Lysates were centrifuged at 14,000 ϫ g for 10 min at 4°C.…”

Section: P53 Phosphorylationmentioning

confidence: 99%

Helicobacter pyloriCagA-Dependent Macrophage Migration Inhibitory Factor Produced by Gastric Epithelial Cells Binds to CD74 and Stimulates Procarcinogenic Events

Beswick

Pinchuk

Suárez

et al. 2006

The Journal of Immunology

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Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has recently been implicated in carcinogenesis. Helicobacter pylori, which is closely linked to gastric cancer, induces the gastric epithelium to produce proinflammatory cytokines, including MIF. MIF can bind to CD74, which we have previously shown to be highly expressed on the surface of gastric epithelial cells (GEC) during H. pylori infection. In this study, we sought to investigate the role of the H. pylori-induced MIF on epithelial proliferation and procarcinogenic events. Upon establishing a role for the H. pylori CagA virulence factor in MIF production, MIF binding to CD74 on GEC was confirmed. rMIF and H. pylori were shown to increase GEC proliferation, which was decreased when cagA− strains were used and when CD74 was blocked by mAbs. Apoptosis was also decreased by MIF, but increased by cagA− strains that induced much lower amounts of MIF than the wild-type bacteria. Furthermore, MIF binding to CD74 was also shown to decrease p53 phosphorylation and up-regulate Bcl-2 expression. This data describes a novel system in which an H. pylori virulence factor contributes to the production of a host factor that in turn up-regulates procarcinogenic events by the gastric epithelium.

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Helicobacter pylori increases proliferation of gastric epithelial cells.

Abstract: The direct and indirect effects of Helicobacter pylori on cell kinetics of gastric epithelial cell line AGS were investigated by flow cytometric analysis of

Cited by 132 publications

References 17 publications

Helicobacter pylori-Induced Chronic Active Gastritis, Intestinal Metaplasia, and Gastric Ulcer in Mongolian Gerbils

Helicobacter pylori-Induced Chronic Active Gastritis, Intestinal Metaplasia, and Gastric Ulcer in Mongolian Gerbils

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

Helicobacter pyloriCagA-Dependent Macrophage Migration Inhibitory Factor Produced by Gastric Epithelial Cells Binds to CD74 and Stimulates Procarcinogenic Events

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