Cutting edge:: The IκB kinase (IKK) inhibitor, NEMO-binding domain peptide, blocks inflammatory injury in murine colitis

Inflammatory mediators such as TNF-alpha, IL-6, and IL-1 are important in the pathogenesis of inflammatory bowel diseases and are regulated by the activation of NF-kappa B. The aim of the present study was to investigate whether the NF-kappa B essential modulator (NEMO)-binding domain (NBD) peptide, which has been shown to block the association of NEMO with the I kappa B kinase beta subunit (IKK beta) and inhibit NF-kappa B activity, reduces inflammatory injury in mice with colitis. Two colitis models were established by the following: 1) inclusion of dextran sulfate sodium salt (DSS) in the drinking water of the mice; and 2) a trinitrobenzene sulfonic acid enema. Marked NF-KB activation and expression of proinflammatory cytokines were observed in colonic tissues. The NBD peptide ameliorated colonic inflammatory injury through the down-regulation of proinflammatory cytokines mediated b NF-kappa B inhibition in both models. These results indicate that an IKK beta-targeted NF-kappa B blockade using the NBD peptide could be an attractive therapeutic approach for inflammatory bowel disease.