A C-Terminal Coiled-Coil Region of CagL is Responsible for Helicobacter Pylori -Induced Il-8 Expression.

Autor:	Wiedemann T; Helmholtz Zentrum München, German Research Center for Environmental Health, Institute for Diabetes and Cancer , Neuherberg, Germany., Hofbaur S; Max-von-Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig Maximilians University , Munich, Germany., Loell E; Max-von-Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig Maximilians University , Munich, Germany., Rieder G; Bavarian Health and Food Safety Authority, Veterinaerstrasse 2 , D-85764 Oberschleissheim, Germany.
Jazyk:	angličtina
Zdroj:	European journal of microbiology & immunology [Eur J Microbiol Immunol (Bp)] 2016 Jul 19; Vol. 6 (3), pp. 186-196. Date of Electronic Publication: 2016 Jul 19 (Print Publication: 2016).
DOI:	10.1556/1886.2016.00020
Abstrakt:	Interleukin-8 (IL-8) is a potent neutrophil-activating chemokine which triggers the infiltration and migration of neutrophils into areas of bacterial infection. Helicobacter pylori -infected patient studies as well as animal models have revealed that H. pylori type I strains carrying an intact cytotoxin-associated gene pathogenicity island ( cag -PAI) with a functional type IV secretion system (T4SS) induce IL-8 expression and secretion in gastric mucosa. This gastric mucosal IL-8 expression correlates with severe histological changes due to H. pylori infection. In the present study, we explored a new recognition pattern on the bacterial adhesion protein CagL inducing IL-8 expression in H. pylori -infected host cells. To analyze the secreted IL-8 concentration, we performed IL-8 enzyme-linked immunosorbent assay (ELISA). To investigate the H. pylori -induced IL-8 expression on the transcriptional level, we transiently transfected gastric epithelial cells (AGS) with a human IL-8 luciferase reporter construct. The results of this study demonstrate that specifically the C-terminal coiled-coil region of the H. pylori CagL protein, a protein described to be located on the tip of the T4SS-pilus, is responsible for several in vitro observations: 1) H. pylori -induced IL-8 secretion via the transforming growth factor (TGF)-α activated epidermal growth factor-receptor (EGF-R) signaling pathway; 2) H. pylori -induced elongation of the cells, a typical CagA-induced phenotype; and 3) the bridging of the T4SS to its human target cells. This novel bacterial-host recognition sequence allows a new insight into how H. pylori induces the inflammatory response in gastric epithelial cells and facilitates the development of precancerous conditions. Competing Interests: The authors have declared that no competing interests exist.
Databáze:	MEDLINE
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