1887

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Volume 69, Issue 3

Editor's Choice N-terminal region of CagA induces IL-8 production in gastric epithelial cells via the β1 integrin receptor Free

Abstract

. is associated with gastrointestinal disease, most notably gastric cancer. Cytotoxin-associated antigen A (CagA), an important virulence factor for 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.

To investigate the effect of CagA (a peptide in the N-terminal CagA) on IL-8 production by gastric epithelial cells.

. CagA 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.

. CagA induced IL-8 expression by AGS cells. IL-8 induction by CagAwas specifically inhibited by ITGB1 deficiency. Notably, CagA activated the phosphorylation of both p38 and ERK1/2, and blocking p38 and ERK1/2 activity significantly reduced IL-8 induction by CagA. ITGB1 deficiency also inhibited the activation of p38 phosphorylation by CagA. Finally, experiments in CagA and/or CagL knockout bacterial lines demonstrated that extracellular CagA might induce IL-8 production by AGS cells.

. Residues 303–456 of the N-terminal region of CagA induce IL-8 production via a CagA–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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): CagA , ERK1/2 , Helicobacter pylori , IL-8 , ITGB1 and p38
Funding
This study was supported by the:
  • Natural Science Foundation of Fujian Province (Award 2018J01837)
    • Principle Award Recipient: Xiaoyan Zhang
  • National Natural Science Foundation of China (Award 81571964)
    • Principle Award Recipient: Feifei She
© 2020 The Authors
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2020-02-25
2024-04-19
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N-terminal region of Helicobacter pylori CagA induces IL-8 production in gastric epithelial cells via the β1 integrin receptor
J. Med. Microbiol. 69, 457 (2020); https://doi.org/10.1099/jmm.0.001088
/content/journal/jmm/10.1099/jmm.0.001088
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