2 research outputs found
Helicobacter pylori CagL dependent induction of gastrin expression via a novel αvβ5-integrin-integrin linked kinase signalling complex
One of the most important hormones in the human stomach is the peptide gastrin. It is mainly required for the regulation of gastric pH but is also involved in growth and differentiation of gastric epithelial cells. In Helicobacter pylori infected patients, gastrin secretion can be upregulated by the pathogen, resulting in hypergastrinaemia. H pylori induced hypergastrinaemia is described as being a major risk factor for the development of gastric adenocarcinoma
A C-terminal coiled-coil region of CagL is responsible for Helicobacter pylori-induced IL-8 expression
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