%0 Journal Article %A Zeng, Bangwei %A Chen, Chu %A Yi, Qingfeng %A Zhang, Xiaoyan %A Wu, Xiangyan %A Zheng, Shurong %A Li, Neng %A She, Feifei %T N-terminal region of Helicobacter pylori CagA induces IL-8 production in gastric epithelial cells via the β1 integrin receptor %D 2020 %J Journal of Medical Microbiology, %V 69 %N 3 %P 457-464 %@ 1473-5644 %R https://doi.org/10.1099/jmm.0.001088 %K p38 %K ERK1/2 %K CagA %K IL-8 %K ITGB1 %K Helicobacter pylori %I Microbiology Society, %X Introduction. Helicobacter pylori is associated with gastrointestinal disease, most notably gastric cancer. Cytotoxin-associated antigen A (CagA), an important virulence factor for H. pylori pathogenicity, induces host cells to release inflammatory factors, especially interleukin-8 (IL-8). The mechanism by which C-terminal CagA induces IL-8 production has been studied extensively, but little is known about the role of the N-terminus. Aim. To investigate the effect of CagA303–456aa (a peptide in the N-terminal CagA) on IL-8 production by gastric epithelial cells. Methodology. CagA303-456aa was produced by a prokaryotic expression system and purified by Strep-tag affinity chromatography. An integrin β1 (ITGB1)-deficient AGS cell line was constructed using the CRISPR/Cas9 technique, and NCTC 11637 cagA and/or cagL knockout mutants were constructed via homologous recombination. The levels of IL-8 production were determined by enzyme-linked immunosorbent assay (ELISA), and p38 and ERK1/2 phosphorylation were examined by Western blot. Results. CagA303-456aa induced IL-8 expression by AGS cells. IL-8 induction by CagA303-456aawas specifically inhibited by ITGB1 deficiency. Notably, CagA303-456aa activated the phosphorylation of both p38 and ERK1/2, and blocking p38 and ERK1/2 activity significantly reduced IL-8 induction by CagA303-456aa. ITGB1 deficiency also inhibited the activation of p38 phosphorylation by CagA303-456aa. Finally, experiments in CagA and/or CagL knockout bacterial lines demonstrated that extracellular CagA might induce IL-8 production by AGS cells. Conclusion. Residues 303–456 of the N-terminal region of CagA induce IL-8 production via a CagA303-456–ITGB1–p38–IL-8 pathway, and ERK1/2 is also involved in the release of IL-8. Extracellular CagA might induce IL-8 production before translocation into AGS cells. %U https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.001088