title: 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.
authors.affiliation: Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea.
authors.forename: Yong-Jae
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea.
authors.forename: Yeji
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Key Laboratory of Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Jingyue
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea.
authors.forename: Se-Hwan
authors.initials: SH
authors.lastname: Paek
authors.affiliation: Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea.
authors.forename: Hyong-Bai
authors.initials: HB
authors.lastname: Kim
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, USA sjin@ufl.edu haunhwan@korea.ac.kr.
authors.forename: Shouguang
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea sjin@ufl.edu haunhwan@korea.ac.kr.
authors.forename: Un-Hwan
authors.initials: UH
authors.lastname: Ha
mesh_terms: D002460:Cell Line; D005408:Flagellin / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D016328:NF-kappa B / Q000378:metabolism; D009701:Nucleoside-Diphosphate Kinase / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D005408:Flagellin; D051057:Proto-Oncogene Proteins c-akt; D009701:Nucleoside-Diphosphate Kinase