The anti-inflammatory compound curcumin inhibits Neisseria gonorrhoeae-induced NF-kappaB signaling, release of pro-inflammatory 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 (TNFalpha), interleukin-6 (IL-6), and IL-8. We identified the immediate early response transcription factor nuclear factor kappaB (NF-kappaB) as a key molecule for the induction of cytokine release. Ngo-induced activation of direct upstream signaling molecules was demonstrated for IkappaB kinase alpha and beta (IKKalpha and IKKbeta) by phosphorylation of IkappaBalpha as a substrate and IKK autophosphorylation. Using dominant negative cDNAs encoding kinase-dead IKKalpha, IKKbeta, and NF-kappaB-inducing kinase (NIK), Ngo-induced NF-kappaB activity was significantly inhibited. Curcumin, the yellow pigment derived from Curcuma longa, inhibited IKKalpha, IKKbeta and NIK, indicating its strong potential to block NF-kappaB-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.
Wessler
Silja
S
Paul-Ehrlich-Institute, D-63225 Langen, Germany.
Muenzner
Petra
P
Meyer
Thomas F
TF
Naumann
Michael
M
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects*; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004789:Enzyme Activation; D006069:Gonorrhea / Q000378:metabolism* / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D003474:Curcumin