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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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

Silja Wessler1 / Petra Muenzner2 / Thomas F. Meyer3 / Michael Naumann4

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Corresponding author

Citation Information: Biological Chemistry. Volume 386, Issue 5, Pages 481–490, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2005.057, July 2005

Publication History

Received:
January 5, 2005
Accepted:
March 7, 2005
Published Online:
2005-07-05

Abstract

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 α (TNFα), interleukin-6 (IL-6), and IL-8. We identified the immediate early response transcription factor nuclear factor κB (NF-κB) as a key molecule for the induction of cytokine release. Ngo-induced activation of direct upstream signaling molecules was demonstrated for IκB kinase α and β (IKKα and IKKβ) by phosphorylation of IκBα as a substrate and IKK autophosphorylation. Using dominant negative cDNAs encoding kinase-dead IKKα, IKKβ, and NF-κB-inducing kinase (NIK), Ngo-induced NF-κB activity was significantly inhibited. Curcumin, the yellow pigment derived from Curcuma longa, inhibited IKKα, IKKβ and NIK, indicating its strong potential to block NF-κB-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.

Keywords: IκB; IκBα kinase; inflammation; innate immune response; NF-κB-inducing kinase

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