title: Helicobacter pylori induces type 4 secretion system-dependent, but CagA-independent activation of IκBs and NF-κB/RelA at early time points.
abstract: Colonization of the gastric epithelium by Helicobacter pylori induces the transcription factor nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) and the innate immune response. Virulent strains of H. pylori carry a cag pathogenicity island (cagPAI), which encodes a type IV secretion system (T4SS). Recent publications have shown controversial data regarding the role of the T4SS and the effector protein cytotoxin associated gene A (CagA), which becomes translocated by the T4SS into the eukaryotic epithelial cell, in H. pylori-induced NF-κB activation. Thus, this study analyses by using three different H. pylori strains (P1, B128 and G27) whether CagA is required to initiate activation of different molecules of inhibitors of kappa B (IκB) and the NF-κB transcription factor RelA. We provide experimental evidence that H. pylori induces phosphorylation of NF-κB inhibitors IκBα, IκBβ and IκBɛ, and degradation of IκBα. Further, H. pylori stimulates phosphorylation of RelA at amino acids S536, S468 and S276, promotes DNA binding of RelA, and interleukin 8 (IL-8) gene expression in a T4SS-, but CagA-independent manner at early time points.
authors: Institute of Experimental Internal Medicine, Otto von Guericke University, 39120 Magdeburg, Germany. Electronic address: Olga.Sokolova@med.ovgu.de.
authors: Olga
authors: O
authors: Sokolova
authors: Marc
authors: M
authors: Borgmann
authors: Cornelia
authors: C
authors: Rieke
authors: Katrin
authors: K
authors: Schweitzer
authors: Hermann-Josef
authors: HJ
authors: Rothkötter
authors: Michael
authors: M
authors: Naumann
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D058947:Bacterial Secretion Systems / Q000276:immunology*; D020868:Gene Silencing; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015533:Transcriptional Activation
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D016328:NF-kappa B; C080866:cagA protein, Helicobacter pylori
keywords: Inflammation; IκBs; RelA phosphorylation; cagPAI pathogenicity island