Lymphotoxin β receptor signalling executes<i>Helicobacter pylori</i>-driven gastric inflammation in a T4SS-dependent manner

Mejías-Luque, Raquel; Zöller, Jessica; Anderl, Florian; Loew-Gil, Elena; Adler, Thure; Engler, Daniela B.; Urban, Sabine; Browning, Jeffrey L.; Müller, Anne; Gerhard, Markus; Heikenwälder, Mathias

doi:10.1136/gutjnl-2015-310783

Cited by 36 publications

(56 citation statements)

References 53 publications

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“…2 The inflammatory reaction triggered by the bacterial infection is a key contributing factor to the development of chronic gastritis. 2 GECs provide the first point of contact between H pylori and the host, and play important roles in inflammatory reactions, thus, a better understanding of the cellular and molecular mechanisms of H pylori-associated chronic gastritis is urgently required. The cagA protein is a 120-140 kDa protein which can be injected into gastric epithelial cells (GECs) via the type IV secretion system (T4SS).…”

Section: Introductionmentioning

confidence: 99%

“…1 Chronic gastritis induced by H pylori can progress to atrophic gastritis, intestinal metaplasia, dysplasia, and ultimately gastric cancer (GC). 2 The inflammatory reaction triggered by the bacterial infection is a key contributing factor to the development of chronic gastritis. 3 The high levels of the inflammatory reaction to H pylori have been directly linked to the presence of microbial virulence factors, mainly the cagA (cytotoxin-associated gene A) protein.…”

Section: Introductionmentioning

confidence: 99%

“…The cagA protein is a 120-140 kDa protein which can be injected into gastric epithelial cells (GECs) via the type IV secretion system (T4SS). 2 GECs provide the first point of contact between H pylori and the host, and play important roles in inflammatory reactions, thus, a better understanding of the cellular and molecular mechanisms of H pylori-associated chronic gastritis is urgently required.…”

Section: Introductionmentioning

confidence: 99%

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Upexpression of BHLHE40 in gastric epithelial cells increases CXCL12 production through interaction with p‐STAT3 in Helicobacter pylori‐associated gastritis

Teng

Zhao

et al. 2019

The FASEB Journal

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BHLHE40, a member of the basic helix-loop-helix transcription factor family, has been reported to play an important role in inflammatory diseases. However, the regulation and function of BHLHE40 in Helicobacter pylori (H pylori)-associated gastritis is unknown. We observed that gastric BHLHE40 was significantly elevated in patients and mice with H pylori infection. Then, we demonstrate that H pyloriinfected GECs express BHLHE40 via cagA-ERK pathway. BHLHE40 translocates to cell nucleus, and then binds to cagA protein-activated p-STAT3 (Tyr705). The complex increases chemotactic factor CXCL12 expression (production). Release of CXCL12 from GECs fosters CD4 + T cell infiltration in the gastric mucosa. Our results identify the cagA-BHLHE40-CXCL12 axis that contributes to inflammatory response in gastric mucosa during H pylori infection.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Upexpression of BHLHE40 in gastric epithelial cells increases CXCL12 production through interaction with p‐STAT3 in Helicobacter pylori‐associated gastritis

Teng

Zhao

et al. 2019

The FASEB Journal

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“…New information was also provided on the mechanisms by which H. pylori virulence factors, including the cag type IV secretion system (T4SS) and vacuolating cytotoxin A (VacA), influence inflammation. Mejías-Luque et al 5 found that the cagT4SS is important in controlling expression of lymphotoxins (LTs). Activation of LT beta receptor (LTβR) signaling led to alternative NF-κB signaling.…”

Section: Epithelial Cell -Helicobacter Pylori Interactionsmentioning

confidence: 99%

Helicobacter: Inflammation, immunology and vaccines

2017

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Helicobacter pylori is usually acquired in early childhood and the infection persists lifelong without causing symptoms. In a small of cases, the infection leads to gastric or duodenal ulcer disease, or gastric cancer. Why disease occurs in these individuals remains unclear, however the host response is known to play a very important part. Understanding the mechanisms involved in maintaining control over the immune and inflammatory response is therefore extremely important. Vaccines against H. pylori have remained elusive but are desperately needed for the prevention of gastric carcinogenesis. This review focuses on research findings which may prove useful in the development of prognostic tests for gastric cancer development, therapeutic agents to control immunopathology, and effective vaccines.

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“…Helicobacter pylori (H. pylori) infects~4.4 billion individuals worldwide and is closely associated with chronic gastritis [1][2][3] . Chronic gastritis induced by H. pylori can progress to atrophic gastritis, intestinal metaplasia, dysplasia, and ultimately gastric cancer (GC) 3 .…”

Section: Introductionmentioning

confidence: 99%

Expression of ETS1 in gastric epithelial cells positively regulate inflammatory response in Helicobacter pylori-associated gastritis

Teng

Cang²,

Mao

et al. 2020

Cell Death Dis

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Gastric epithelial cells (GECs) provide the first point of contact of the host by Helicobacter pylori (H. pylori), and the interaction between H. pylori and GECs plays a critical role in H. pylori-associated diseases. Aberrant expression of transcription factors (TFs) contributes to the pathogenesis of inflammatory disorders, including H. pylori-associated gastritis. ETS (E26 transformation specific) transcription factor family is one of the largest families of evolutionarily conserved TFs, regulating critical functions during cell homeostasis. We screened ETS family gene expression in H. pylori-infected mouse and human GECs and found that ETS1 (ETS proto-oncogene 1, transcription factor) expression was highly affected by H. pylori infection. Then, we reported that ETS1 was induced in GECs by H. pylori via cagA activated NF-κB pathway. Notably, we demonstrated that proinflammatory cytokines IL-1β and TNFα have synergistic effects on ETS1 expression during H. pylori infection in an NF-κB-pathway-dependent manner. RNA-seq assay and Gene-ontology functional analysis revealed that ETS1 positively regulate inflammatory response during H. pylori infection. Increased ETS1 is also detected in the gastric mucosa of mice and patients with H. pylori infection. Collectively, these data showed that ETS1 may play an important role in the pathogenesis of H. pylori-associated gastritis.

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Lymphotoxin β receptor signalling executesHelicobacter pylori-driven gastric inflammation in a T4SS-dependent manner

Cited by 36 publications

References 53 publications

Upexpression of BHLHE40 in gastric epithelial cells increases CXCL12 production through interaction with p‐STAT3 in Helicobacter pylori‐associated gastritis

Upexpression of BHLHE40 in gastric epithelial cells increases CXCL12 production through interaction with p‐STAT3 in Helicobacter pylori‐associated gastritis

Helicobacter: Inflammation, immunology and vaccines

Expression of ETS1 in gastric epithelial cells positively regulate inflammatory response in Helicobacter pylori-associated gastritis

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