Journal of Microbiology

, Volume 55, Issue 4, pp 311–317 | Cite as

Cot kinase plays a critical role in Helicobacter pylori-induced IL-8 expression

Microbial Pathogenesis and Host-Microbe Interaction

Abstract

Helicobacter pylori is a major pathogen causing various gastric diseases including gastric cancer. Infection of H. pylori induces pro-inflammatory cytokine IL-8 expression in gastric epithelial cells in the initial inflammatory process. It has been known that H. pylori can modulate Ras-Raf-Mek-Erk signal pathway for IL-8 induction. Recently, it has been shown that another signal molecule, cancer Osaka thyroid oncogene/tumor progression locus 2 (Cot/Tpl2) kinase, activates Mek and Erk and plays a role in the Erk pathway, similar to MAP3K signal molecule Raf kinase. Therefore, the objective of this study was to determine whether Cot kinase might be involved in IL-8 induction caused by H. pylori infection. AGS gastric epithelial cells were infected by H. pylori strain G27 or its isogenic mutants lacking cagA or type IV secretion system followed by treatment with Cot kinase inhibitor (KI) or siRNA specific for Cot kinase. Activation of Erk was assessed by Western blot analysis and expression of IL-8 was measured by ELISA. Treatment with Cot KI reduced both transient and sustained Erk activation. It also reduced early and late IL-8 secretion in the gastric epithelial cell line. Furthermore, siRNA knockdown of Cot inhibited early and late IL-8 secretion induced by H. pylori infection. Taken together, these results suggest that Cot kinase might play a critical role in H. pylori type IV secretion apparatus-dependent early IL-8 secretion and CagA-dependent late IL-8 secretion as an alternative signaling molecule in the Erk pathway.

Keywords

Helicobacter pylori cot erk activation IL-8 mapk pathway 

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Copyright information

© The Microbiological Society of Korea and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Oral Biology, Oral Science Research Center, BK21 Plus ProjectYonsei University College of DentistrySeoulRepublic of Korea
  2. 2.Microbiology and Molecular Biology, Key Laboratory of Oral Medicine, Guangzhou Institute of Oral DiseaseStomatology Hospital of Guangzhou Medical UniversityGuangzhouP. R. China

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