Helicobacter pylori induces direct activation of the lymphotoxin beta receptor and non-canonical nuclear factor-kappa B signaling

Publication date: Available online 9 January 2018 Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Author(s): Michael Hartmut Feige, Michael Vieth, Olga Sokolova, Christian Täger, Michael Naumann The pathogen Helicobacter pylori, which infects half of the world's population, is a major risk factor for the development of gastric diseases including chronic gastritis and gastric cancer. Among H. pylori's virulence factors is the cytotoxin-associated gene pathogenicity island (cagPAI), which encodes for a type IV secretion system (T4SS). The T4SS induces fast canonical nuclear factor-kappa B (NF-κB) signaling, a major factor increasing inflammation, supressing apoptotic cell death and thereby promoting the development of neoplasia. However, H. pylori's capability to mediate fast non-canonical NF-κB signaling is unresolved, despite a contribution of non-canonical NF-κB signaling to gastric cancer has been suggested. We analyzed signaling elements within non-canonical NF-κB in response to H. pylori in epithelial cell lines by immunoprecipitation, immunoblot, electrophoretic mobility shift assay and RNA interference knockdown. In addition, tissue samples of H. pylori-infected patients were investigated by immunohistochemistry. Here, we provide evidence for a T4SS-dependent direct activation of non-canonical NF-κB signaling. We identified the lymphotoxin beta receptor (LTβR) to elicit the fast release of NF-κB inducing kinase (NIK) from the receptor...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research