Projects per year
Abstract
The Gram-negative bacterium, Helicobacter pylori, causes chronic gastritis, peptic ulcers, and gastric cancer in humans. Although the gastric epithelium is the primary site of H. pylori colonization, H. pylori can gain access to deeper tissues. Concurring with this notion, H. pylori has been found in the vicinity of endothelial cells in gastric submucosa. Endothelial cells play crucial roles in innate immune response, wound healing and tumorigenesis. This study examines the molecular mechanisms by which H. pylori interacts with and triggers inflammatory responses in endothelial cells. We observed that H. pylori infection of primary human endothelial cells stimulated secretion of the key inflammatory cytokines, interleukin-6 (IL-6) and interleukin-8 (IL-8). In particular, IL-8, a potent chemokine and angiogenic factor, was secreted by H. pylori-infected endothelial cells to levels ~10- to 20-fold higher than that typically observed in H. pylori-infected gastric epithelial cells. These inflammatory responses were triggered by the H. pylori type IV secretion system (T4SS) and the T4SS-associated adhesin CagL, but not the translocation substrate CagA. Moreover, in contrast to integrin α5β1 playing an essential role in IL-8 induction by H. pylori upon infection of gastric epithelial cells, both integrin α5β1 and integrin αvβ3 were dispensable for IL-8 induction in H. pylori-infected endothelial cells. However, epidermal growth factor receptor (EGFR) is crucial for mediating the potent H. pylori-induced IL-8 response in endothelial cells. This study reveals a novel mechanism by which the H. pylori T4SS and its adhesin subunit, CagL, may contribute to H. pylori pathogenesis by stimulating the endothelial innate immune responses, while highlighting EGFR as a potential therapeutic target for controlling H. pylori-induced inflammation.
Original language | English |
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Article number | 22 |
Number of pages | 15 |
Journal | Frontiers in Cellular and Infection Microbiology |
Volume | 8 |
Issue number | FEB |
DOIs | |
Publication status | Published - 6 Feb 2018 |
Keywords
- CagL
- Endothelial cells
- Helicobacter
- HUVECs
- Inflammation
- Interleukin-8
- Type IV secretion
Projects
- 1 Finished
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Roles of integrin receptors and the Helicobacter pylori protein CagL in gastritis and gastric cancer
Kwok-Schuelein, T. (Primary Chief Investigator (PCI))
NHMRC - National Health and Medical Research Council (Australia)
5/01/09 → 31/12/12
Project: Research