<i>Helicobacter pylori</i> Activates IL‐6‐STAT3 Signaling in Human Gastric Cancer Cells: Potential Roles for Reactive Oxygen Species

Piao, Juan‐Yu; Lee, Hee Geum; Kim, Su-Jung; Kim, Do-Hee; Han, Heon-Seok; Ngo, Hoang-Kieu-Chi; Park, Sin-Aye; Woo, Jeong-Hwa; Lee, Jeong-Sang; Na, Hye-Kyung; Cha, Young‐Nam; Surh, Young‐Joon

doi:10.1111/hel.12298

Cited by 62 publications

(52 citation statements)

References 38 publications

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“…Upregulated expression of IL-6 has been noted previously in O. viverrini (16) and H. pylori single infections (17), which might synergistically induce inflammation-mediated liver injury through oxidative stress (12,17). As a result of this, the lipopolysaccharide of bacteria, including H. pylori, can induce TGF-␤ signaling through Toll-like receptor 4 (18), contributing to fibrogenesis.…”

Section: Discussionmentioning

confidence: 84%

Coinfection with Helicobacter pylori and Opisthorchis viverrini Enhances the Severity of Hepatobiliary Abnormalities in Hamsters

et al. 2017

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Persistent infection with Opisthorchis viverrini causes hepatobiliary abnormalities, predisposing infected individuals to cholangiocarcinoma (CCA). In addition, Helicobacter pylori is highly prevalent in most countries and is a possible risk factor for CCA; however, its role in enhancing hepatobiliary abnormality is unclear. Here, we investigated the effects of coinfection with H. pylori and O. viverrini on hepatobiliary abnormality. Hamsters were divided into four groups: (i) normal, (ii) H. pylori infected (HP), (iii) O. viverrini infected (OV), and (iv) O. viverrini and H. pylori infected (OVϩHP). At 6 months postinfection, PCR and immunohistochemistry were used to test for the presence of H. pylori in the stomach, gallbladder, and liver. In the liver, H. pylori was detected in the following order: OVϩHP, 5 of 8 (62.5%); HP, 2 of 5 (40%); OV, 2 of 8 (25%). H. pylori was not detected in normal (control) liver tissues. Coinfection induced the most severe hepatobiliary abnormalities, including periductal fibrosis, cholangitis, and bile duct hyperplasia, leading to a significantly decreased survival rate of experimental animals. The greatest thickness of periductal fibrosis was associated with a significant increase in fibrogenesis markers (expression of alpha smooth muscle actin and transforming growth factor beta). Quantitative reverse transcription-PCR revealed that the highest expression levels of genes for proinflammatory cytokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor alpha) were also observed in the OVϩHP group. These results suggest that coinfection with H. pylori and O. viverrini increased the severity of hepatobiliary abnormalities to a greater extent than either single infection did.

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Section: Discussionmentioning

confidence: 84%

Coinfection with Helicobacter pylori and Opisthorchis viverrini Enhances the Severity of Hepatobiliary Abnormalities in Hamsters

et al. 2017

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“…demonstrated that the oxidative burst induced by H. pylori in human gastric epithelial cells is responsible for the PI3K/AKT1-dependent expression of the transcription factor Snail family zinc finger 1 (SNAI1, also known as SNAIL) [111], which is essential for epithelial-mesenchymal transition and therefore in gastric cancer progression and metastasis. Additionally, it has been shown that the transcription factor signal transducer and activator of transcription 3 (STAT3), which plays a major function in inflammation and angiogenesis, is also induced in gastric epithelial cells via upregulated autocrine IL-6 signaling, partially mediated by endogenous ROS [112]. Moreover, α-lipoic acid, a naturally occurring thiol compound that exhibits antioxidant properties, inhibits NOX-derived ROS production in AGS cells and concomitantly dampens NF-κB and AP-1 activation and expression of the oncogenes β-catenin (CTNNB1) and MYC [113].…”

Section: Endogenous Effect Of Ros On the Hostmentioning

confidence: 99%

Polyamine- and NADPH-dependent generation of ROS during Helicobacter pylori infection: A blessing in disguise

Gobert

Wilson

2017

Free Radical Biology and Medicine

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Helicobacter pylori is a Gram-negative bacterium that specifically colonizes the gastric ecological niche. During the infectious process, which results in diseases ranging from chronic gastritis to gastric cancer, the host response is characterized by the activation of the innate immunity of gastric epithelial cells and macrophages. These cells thus produce effector molecules such as reactive oxygen species (ROS) to counteract the infection. The generation of ROS in response to H. pylori involves two canonical pathways: 1) the NADPH-dependent reduction of molecular oxygen to generate O2•−, which can dismute to generate ROS; and 2) the back-conversion of the polyamine spermine into spermidine through the enzyme spermine oxidase, leading to H2O2 production. Although these products have the potential to affect the survival of bacteria, H. pylori has acquired numerous strategies to counteract their deleterious effects. Nonetheless, ROS-mediated oxidative DNA damage and mutations may participate in the adaptation of H. pylori to its ecological niche. Lastly, ROS have been shown to play a major role in the development of the inflammation and carcinogenesis. It is the purpose of this review to summarize the literature about the production of ROS during H. pylori infection and their role in this infectious gastric disease.

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“…(2016) have demonstrated that the oxidative burst induced by H. pylori in human gastric epithelial cells is responsible for the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase 1 (AKT1)/glycogen synthase kinase 3 beta (GSK3B)-dependent expression of the transcription factor Snail (SNAI1) (Ngo et al 2016), which is essential for epithelial-mesenchymal transition and therefore in gastric cancer progression and metastasis. Additionally, it has been shown that the transcription factor signal transducer and activator of transcription 3 (STAT3), which plays a major function in inflammation and angiogenesis, is also induced in gastric epithelial cells via upregulated autocrine IL-6 signaling, partially mediated by endogenous ROS (Piao et al 2016). Lastly, α-lipoic acid, a naturally occurring thiol compound that exhibits antioxidant properties, inhibits NADPH oxidase-derived ROS production in AGS cells and concomitantly dampens NF-κB and AP-1 activation and expression of the oncogenes β-catenin (CTNNB1) and c-Myc (MYC) (Byun et al 2014).…”

Section: Induction and Role Of Rosmentioning

confidence: 99%

Human and Helicobacter pylori Interactions Determine the Outcome of Gastric Diseases

Gobert

Wilson

2017

Current Topics in Microbiology and Immunology

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The innate immune response is a critical hallmark of Helicobacter pylori infection. Epithelial and myeloid cells produce effectors, including the chemokine CXCL8, reactive oxygen species (ROS), and nitric oxide (NO), in response to bacterial components. Mechanistic and epidemiologic studies have emphasized that dysregulated and persistent release of these products leads to the development of chronic inflammation and to the molecular and cellular events related to carcinogenesis. Moreover, investigations in H. pylori-infected patients about polymorphisms of the genes encoding CXCL8 and inducible NO synthase, and epigenetic control of the ROS-producing enzyme spermine oxidase, have further proven that overproduction of these molecules impacts the severity of gastric diseases. Lastly, the critical effect of the crosstalk between the human host and the infecting bacterium in determining the severity of H. pylori-related diseases has been supported by phylogenetic analysis of the human population and their H. pylori isolates in geographic areas with varying clinical and pathologic outcomes of the infection.

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Helicobacter pylori Activates IL‐6‐STAT3 Signaling in Human Gastric Cancer Cells: Potential Roles for Reactive Oxygen Species

Abstract: H. pylori-induced STAT3 activation is mediated, at least in part, through ROS-induced upregulation of IL-6 expression. These findings provide a novel molecular mechanism responsible for H. pylori-induced gastritis and gastric carcinogenesis.

Cited by 62 publications

References 38 publications

Coinfection with Helicobacter pylori and Opisthorchis viverrini Enhances the Severity of Hepatobiliary Abnormalities in Hamsters

Coinfection with Helicobacter pylori and Opisthorchis viverrini Enhances the Severity of Hepatobiliary Abnormalities in Hamsters

Polyamine- and NADPH-dependent generation of ROS during Helicobacter pylori infection: A blessing in disguise

Human and Helicobacter pylori Interactions Determine the Outcome of Gastric Diseases

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