Association between Helicobacter pylori infection and interleukin 1  polymorphism predispose to CpG island methylation in gastric cancer

Chan, Annie On On; Chu, Kent‐Man; Huang, Camy; Lam, Kwok Fai; Leung, Suet Yi; Sun, Yun; Ko, Samuel; Xia, Harry H.X.; Cho, Chi Hin; Hui, W. M.; Lam, Shiu Kum; Rashid, Asif

doi:10.1136/gut.2006.113258

Cited by 40 publications

(30 citation statements)

References 10 publications

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“…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. 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.…”

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confidence: 99%

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confidence: 99%

“…6,7 OPN, functioning as chemoattractive Th1 cytokine, promotes the migration of inflammatory cells. 7,13 Clinically, increased plasma OPN levels were proven in many chronic inflammatory diseases such as Crohn's disease and rheumatoid arthritis and various cancers including gastric cancer. 7 A recent study showed that increased gastric OPN expression in response to HP infection correlates well with the degree of gastric inflammation and intestinal metaplasia in humans.…”

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confidence: 99%

“…7,13 Clinically, increased plasma OPN levels were proven in many chronic inflammatory diseases such as Crohn's disease and rheumatoid arthritis and various cancers including gastric cancer. 7 A recent study showed that increased gastric OPN expression in response to HP infection correlates well with the degree of gastric inflammation and intestinal metaplasia in humans. 14 However, the exact functional roles of OPN in HP-induced gastritis have not yet been fully investigated.…”

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confidence: 99%

“…14 However, the exact functional roles of OPN in HP-induced gastritis have not yet been fully investigated. Previous reports have focused on the role of OPN in macrophage functions in various immunological disorders, 7 whereas the role of OPN in epithelial cells in response to infectious pathogens, such as HP, has been not studied.…”

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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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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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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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H. pyloriInfection – The Route from Inflammation to Cancer

Chiba

Marusawa

Seno

et al. 2010

Bacterial Virulence

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Helicobacter pylori induces promoter methylation of E‐cadherin via interleukin‐1β activation of nitric oxide production in gastric cancer cells

Huang

Chan

Rashid

et al. 2012

Cancer

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BACKGROUND:Helicobacter pylori infection causes gastric mucosal inflammatory responses, resulting in up-regulation of interleukin1b (IL-1b) and overproduction of mutagenic nitric oxide (NO). The authors previously demonstrated that IL-1b plays an important role in H. pylori-induced E-cadherin (E-cad) methylation. Here, they extend the study to investigate the downstream effect of IL-1b on H. pylori-induced gastric inflammation and aberrant DNA methylation. METHODS: Human gastric cancer cell lines (MKN7, MKN74, and TMK-1) with and without pretreatment of IL-1 receptor antagonist (IL-1ra) were treated with IL-1b or infected with H. pylori. Promoter methylation status of E-cad was examined by methylation-specific polymerase chain reaction (PCR). Expression of E-cad, inducible nitric oxide synthase (iNOS), and nuclear factor jB (NFjB) was assessed by quantitative reverse transcriptase PCR, Western blotting, or immunofluorescence. NO production and total DNA methyltransferase (DNMT) activity were assayed fluorometrically. RESULTS: Both IL-1b treatment and H. pylori infection-induced E-cad methylation led to a decrease in E-cad expression at both mRNA and protein levels. Total DNMT enzymatic activity was significantly elevated in treated cells, accounting for the observed E-cad methylation induction. Increased expression of NFjB was accompanied by up-regulation of iNOS and production of NO in treated cells. Reversal of all these phenomena in cells pretreated with IL-1ra suggested H. pylori-induced E-cad methylation via IL-1b stimulation of the NFjB transcriptional system, leading to activation of DNMT activity by NO production. CONCLUSIONS: These findings reveal a previously unknown effect of IL-1b and NO on H. pylori-induced aberrant DNA methylation. This possible pathway indicates the role of NO in epigenetic modification that links inflammation to carcinogenesis. Cancer 2012;118:4969-80.

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Association between Helicobacter pylori infection and interleukin 1 polymorphism predispose to CpG island methylation in gastric cancer

Cited by 40 publications

References 10 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

H. pyloriInfection – The Route from Inflammation to Cancer

Helicobacter pylori induces promoter methylation of E‐cadherin via interleukin‐1β activation of nitric oxide production in gastric cancer cells

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