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Nucleoside diphosphate kinase and flagellin from Pseudomonas aeruginosa induce interleukin 1 expression via the Akt/NF-κB signaling pathways.

Abstract
Inflammatory responses are a first line of host defense against a range of invading pathogens, consisting of the release of proinflammatory cytokines followed by attraction of polymorphonuclear neutrophils (PMNs) to the site of inflammation. Among the many virulence factors that contribute to the pathogenesis of infections, nucleoside diphosphate kinase (Ndk) mediates bacterially induced toxicity against eukaryotic cells. However, no study has examined how Ndk affects inflammatory responses. The present study examined the mechanisms by which Pseudomonas aeruginosa activates inflammatory responses upon infection of cells. The results showed that bacterial Ndk, with the aid of an additional bacterial factor, flagellin, induced expression of the proinflammatory cytokines interleukin-1α (IL-1α) and IL-1β. Cytokine induction appeared to be dependent on the kinase activity of Ndk and was mediated via the NF-κB signaling pathway. Notably, Ndk activated the Akt signaling pathway, which acts upstream of NF-κB, as well as caspase-1, which is a key component of inflammasome. Thus, this study demonstrated that P. aeruginosa, through the combined effects of Ndk and flagellin, upregulates the expression of proinflammatory cytokines via the Akt/NF-κB signaling pathways.
AuthorsYong-Jae Kim, Jung-Hoon Lee, Yeji Lee, Jingyue Jia, Se-Hwan Paek, Hyong-Bai Kim, Shouguang Jin, Un-Hwan Ha
JournalInfection and immunity (Infect Immun) Vol. 82 Issue 8 Pg. 3252-60 (Aug 2014) ISSN: 1098-5522 [Electronic] United States
PMID24866792 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Interleukin-1
  • NF-kappa B
  • Flagellin
  • Proto-Oncogene Proteins c-akt
  • Nucleoside-Diphosphate Kinase
Topics
  • Cell Line
  • Flagellin (immunology)
  • Humans
  • Interleukin-1 (biosynthesis)
  • Macrophages (immunology, microbiology)
  • NF-kappa B (metabolism)
  • Nucleoside-Diphosphate Kinase (immunology)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Pseudomonas aeruginosa (immunology)
  • Signal Transduction

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