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.