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B and Activator Protein 1 and the Induction of
Inflammatory Cytokines
By
From the * Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, 10117 Berlin;
and We have studied the effect of human bacterial pathogen Neisseria gonorrhoeae (Ngo) on the activation of nuclear factor (NF)-
Max-Planck-Institut für Biologie, Abteilung Infektionsbiologie, 72076 Tübingen, Germany
B and the transcriptional activation of inflammatory cytokine
genes upon infection of epithelial cells. During the course of infection, Ngo, the etiologic agent
of gonorrhea, adheres to and penetrates mucosal epithelial cells. In vivo, localized gonococcal
infections are often associated with a massive inflammatory response. We observed upregulation of several inflammatory cytokine messenger RNAs (mRNAs) and the release of the proteins in Ngo-infected epithelial cells. Moreover, infection with Ngo induced the formation of a NF-B DNA-protein complex and, with a delay in time, the activation of activator protein 1, whereas basic leucine zipper transcription factors binding to the cAMP-responsive element or
CAAT/enhancer-binding protein DNA-binding sites were not activated. In supershift assays using NF-B-specific antibodies, we identified a NF-B p50/p65 heterodimer. The NF-B
complex was formed within 10 min after infection and decreased 90 min after infection. Synthesis of tumor necrosis factor 
and interluekin (IL)-1
occurred at later times and therefore
did not account for NF-B activation. An analysis of transiently transfected IL-6 promoter deletion constructs suggests that NF-B plays a crucial role for the transcriptional activation of
the IL-6 promoter upon Ngo infection. Inactivation of NF-B conferred by the protease inhibitor N-tosyl-L-phenylalanine chloromethyl ketone inhibited mRNA upregulation of most, but
not all, studied cyctokine genes. Activation of NF-B and cytokine mRNA upregulation also
occur in Ngo-infected epithelial cells that were treated with cytochalasin D, indicating an extracellular signaling induced before invasion.
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