title: A C-Terminal Coiled-Coil Region of CagL is Responsible forHelicobacter Pylori-Induced Il-8 Expression.
abstract: 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 thatH. pyloritype 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 toH. pyloriinfection. In the present study, we explored a new recognition pattern on the bacterial adhesion protein CagL inducing IL-8 expression inH. pylori-infected host cells. To analyze the secreted IL-8 concentration, we performed IL-8 enzyme-linked immunosorbent assay (ELISA). To investigate theH. 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 theH. pyloriCagL protein, a protein described to be located on the tip of the T4SS-pilus, is responsible for severalin vitroobservations: 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 howH. pyloriinduces the inflammatory response in gastric epithelial cells and facilitates the development of precancerous conditions.
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute for Diabetes and Cancer , Neuherberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Wiedemann
authors.affiliation: Max-von-Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig Maximilians University , Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hofbaur
authors.affiliation: Max-von-Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig Maximilians University , Munich, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Loell
authors.affiliation: Bavarian Health and Food Safety Authority, Veterinaerstrasse 2 , D-85764 Oberschleissheim, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Rieder
keywords: CagL; Helicobacter pylori; IL-8; coiled-coil