Interleukin-1β induced by Helicobacter pylori infection enhances mouse gastric carcinogenesis

Shigematsu, Yasuyuki; Niwa, Tohru; Rehnberg, Emil; Toyoda, Takeshi; Yoshida, Shigetoshi; Mori, Akiko; Wakabayashi, Mika; Iwakura, Yoichiro; Ichinose, Masakazu; Kim, Yong Joon; Ushijima, Toshikazu

doi:10.1016/j.canlet.2013.07.034

Cited by 64 publications

(61 citation statements)

References 54 publications

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“…25,26 Notably, there is considerable evidence that elevated expression of IL-1β, IFN-γ, and TNF-α are associated with chronic gastritis and gastric cancer development following HP infection. 7,11,25,27,28 Our study revealed that OPN expression was elevated in response to HP infection, and OPN depletion decreased production of these cytokines in both gastric epithelial cells and macrophages during HP infection. These results suggest that OPN is an important mediator of proinflammatory cytokine production during HP infection.…”

Section: Discussionmentioning

confidence: 57%

“…11,23,24 OPN KD AGS and NCC-S1M cells showed decreased cell proliferation compared with shRNA control cells following exposure to IL-1β and TNF-α for 24 h (Figure 6a). In addition, compared with shRNA control cells, OPN KD AGS and S1M cells showed an attenuation of the increase in the mitogen-activated protein kinase (MAPK)-related molecule, phosphorylated Akt, and Erk following exposure to IL-1β and TNF-α treatment (Figures 6b-e).…”

Section: Opn Deficiency Inhibits the Proliferation Of Gastricmentioning

confidence: 99%

“…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. 12 The interaction between gastric epithelial cells and infiltrating macrophages during HP infection might play an important role in the development of gastritis and HP-related pathogenic changes in gastric epithelial cells.…”

mentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 57%

Section: Opn Deficiency Inhibits the Proliferation Of Gastricmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…IL-1β is a potent inflammatory mediator that has a significant role in initiating and amplifying the inflammatory response against Helicobacter pylori infection (4). The present authors and others have previously demonstrated that IL-1β induced by H. pylori infection promotes gastric carcinogenesis (5,6). Furthermore, the significant role of IL-1β in increasing the risk of gastric inflammation and cancer has been demonstrated by using a transgenic model overexpressing human IL-1β protein (7).…”

Section: Introductionmentioning

confidence: 52%

“…However, the present study provides an improved insight into the role of NO in the IL-1β activated methylation-dependent silencing pathway that may link inflammation with gastric carcinogenesis. Previous studies have reported that IL-1R1 -/ -mice demonstrate attenuated infiltration of inflammatory cells in the stomach with H. pylori infection compared with WT mice (5,6). Among the infiltrating inflammatory cells in H. pylori-infected gastric mucosa, the IL-1R1 -/ -mice demonstrated a significantly reduced number of macrophages and neutrophils compared with the WT mice.…”

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confidence: 83%

Interleukin-1β increases the risk of gastric cancer through induction of aberrant DNA methylation in a mouse model

et al. 2016

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Abstract. Interleukin-1β (IL-1β) has a significant role in chronic gastric inflammation and manifestations of gastric diseases. The present study aimed to elucidate the specific role of IL-1β in induction of DNA methylation using IL-1 receptor type 1 knockout (IL-1R1 -/ -) mice. In the present study, wild-type (WT) and IL-1R1 -/ -mice were injected with IL-1β (5 µg/kg/day). Serum levels of IL-1β, interleukin-6 (IL-6) and nitric oxide (NO) were measured by enzyme-linked immunosorbent or NO assays. E-cadherin (E-cad) methylation status and messenger (m)RNA expression of IL-1β, IL-6, E-cad and inducible nitric oxide synthase (iNOS) were analyzed.

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The Role of Host Genetic Polymorphisms in Helicobacter pylori Mediated Disease Outcome

Clyne

Rowland

2019

Advances in Experimental Medicine and Biology

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Interleukin-1β induced by Helicobacter pylori infection enhances mouse gastric carcinogenesis

Cited by 64 publications

References 54 publications

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

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

Interleukin-1β increases the risk of gastric cancer through induction of aberrant DNA methylation in a mouse model

The Role of Host Genetic Polymorphisms in Helicobacter pylori Mediated Disease Outcome

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