Please use this identifier to cite or link to this item: https://doi.org/10.3389/fcimb.2018.00022
Title: Helicobacter pylori type IV secretion system and its adhesin subunit, CagL, mediate potent inflammatory responses in primary human endothelial cells
Authors: Tafreshi, M.
Guan, J. 
Gorrell, R.J.
Chew, N.
Xin, Y.
Deswaerte, V.
Rohde, M.
Daly, R.J.
Peek, R.M.
Jenkins, B.J.
Davies, E.M.
Kwok, T.
Keywords: CagL
Endothelial cells
Helicobacter
HUVECs
Inflammation
Interleukin-8
Type IV secretion
Issue Date: 2018
Publisher: Frontiers Media S.A.
Citation: Tafreshi, M., Guan, J., Gorrell, R.J., Chew, N., Xin, Y., Deswaerte, V., Rohde, M., Daly, R.J., Peek, R.M., Jenkins, B.J., Davies, E.M., Kwok, T. (2018). Helicobacter pylori type IV secretion system and its adhesin subunit, CagL, mediate potent inflammatory responses in primary human endothelial cells. Frontiers in Cellular and Infection Microbiology 8 (FEB) : 22. ScholarBank@NUS Repository. https://doi.org/10.3389/fcimb.2018.00022
Rights: Attribution 4.0 International
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 ?5?1 playing an essential role in IL-8 induction by H. pylori upon infection of gastric epithelial cells, both integrin ?5?1 and integrin ?v?3 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. © 2018 Tafreshi, Guan, Gorrell, Chew, Xin, Deswaerte, Rohde, Daly, Peek, Jenkins, Davies, and Kwok.
Source Title: Frontiers in Cellular and Infection Microbiology
URI: https://scholarbank.nus.edu.sg/handle/10635/212556
ISSN: 2235-2988
DOI: 10.3389/fcimb.2018.00022
Rights: Attribution 4.0 International
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