The anti-inflammatory compound curcumin inhibits Neisseria gonorrhoeae-induced NF-κB signaling, release of proinflammatory cytokines/chemokines and attenuates adhesion in late infection

Neisseria gonorrhoeae (Ngo) is a Gram-negative pathogenic bacterium responsible for an array of diseases ranging from urethritis to disseminated gonococcal infections. Early events in the establishment of infection involve interactions between Ngo and the mucosal epithelium, which induce a local inflammatory response. Here we analyzed the molecular mechanism involved in the Ngo-induced induction of the proinflammatory cytokines tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), and IL-8. We identified the immediate early response transcription factor nuclear factor kappa B (NF-kappa B) as a key molecule for the induction of cytokine release. Ngo-induced activation of direct upstream signaling molecules was demonstrated for I kappa B kinase alpha and beta (IKK alpha and IKK beta) by phosphorylation Of I kappa B alpha as a substrate and IKK autophosphorylation. Using dominant negative cDNAs encoding kinase-dead IKK alpha, IKK beta, and NF-kappa B-inducing kinase (NIK), Ngo-induced NF-kappa B activity was significantly inhibited. Curcumin, the yellow pigment derived from Curcuma longa, inhibited IKK alpha, IKK beta and NIK, indicating its strong potential to block NF-kappa B-mediated cytokine release and the innate immune response. In addition to the inhibition of Ngo-induced signaling, curcumin treatment of cells completely abolished the adherence of bacteria to cells in late infection, underlining the high potential of curcumin as an anti-microbial compound without cytotoxic side effects.