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

 Sungil Jang  ;  Jinmoon Kim  ;  Jeong-Heon Cha 
 JOURNAL OF MICROBIOLOGY, Vol.55(4) : 311-317, 2017 
Journal Title
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Blotting, Western ; Cell Line ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells/microbiology* ; Epithelial Cells/physiology* ; Extracellular Signal-Regulated MAP Kinases/analysis ; Helicobacter pylori/immunology* ; Humans ; Interleukin-8/metabolism* ; MAP Kinase Kinase Kinases/metabolism* ; MAP Kinase Signaling System ; Proto-Oncogene Proteins/metabolism*
Helicobacter pylori ; IL-8 ; cot ; erk activation ; mapk pathway
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.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jin Moon(김진문)
Jang, Sungil(장성일) ORCID logo https://orcid.org/0000-0001-6144-6899
Cha, Jung Heon(차정헌) ORCID logo https://orcid.org/0000-0002-9385-2653
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