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Ca 2+ /calmodulin‐dependent kinase II contributes to inhibitor of nuclear factor‐kappa B kinase complex activation in Helicobacter pylori infection
Author(s) -
Maubach Gunter,
Sokolova Olga,
Wolfien Markus,
Rothkötter HermannJosef,
Naumann Michael
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28148
Subject(s) - iκb kinase , kinase , helicobacter pylori , nfkb1 , biology , calmodulin , proinflammatory cytokine , protein kinase a , cancer research , transcription factor , nf κb , inflammation , immunology , microbiology and biotechnology , biochemistry , enzyme , genetics , gene
Helicobacter pylori, a class I carcinogen, induces a proinflammatory response by activating the transcription factor nuclear factor‐kappa B (NF‐κB) in gastric epithelial cells. This inflammatory condition could lead to chronic gastritis, which is epidemiologically and biologically linked to the development of gastric cancer. So far, there exists no clear knowledge on how H. pylori induces the NF‐κB‐mediated inflammatory response. In our study, we investigated the role of Ca 2+ /calmodulin‐dependent kinase II (CAMKII), calmodulin, protein kinases C (PKCs) and the CARMA3‐Bcl10‐MALT1 (CBM) complex in conjunction with H. pylori ‐induced activation of NF‐κB via the inhibitor of nuclear factor‐kappa B kinase (IKK) complex. We use specific inhibitors and/or RNA interference to assess the contribution of these components. Our results show that CAMKII and calmodulin contribute to IKK complex activation and thus to the induction of NF‐κB in response to H. pylori infection, but not in response to TNF‐α. Thus, our findings are specific for H. pylori infected cells. Neither the PKCs α, δ, θ, nor the CBM complex itself is involved in the activation of NF‐κB by H. pylori . The contribution of CAMKII and calmodulin, but not PKCs/CBM to the induction of an inflammatory response by H. pylori infection augment the understanding of the molecular mechanism involved and provide potential new disease markers for the diagnosis of gastric inflammatory diseases including gastric cancer.