Selective inhibitors of nuclear factor-kappaB activation and uses thereof

摘要

The present invention provides cell permeable NF-kappaB inhibitors consist of a polypeptide derived from the p65 subunit of NF-kappaB and a protein transduction domain derived from antennapedia third helix sequence. The inhibitor suppressed NF-kappaB activation induced by TNF, LPS, IL-1, okadaic acid, PMA, H₂O₂ and cigarette smoke condensate. NF-kappaB-regulated reporter gene expression induced by TNF, TNFR1, TRADD, TRAF2, NIK, IKK and p65 was suppressed by the inhibitor. The inhibitor enhanced TNF- and chemotherapeutic agent-induced apoptosis. Overall these results demonstrate a NF-kappaB inhibitor that can selectively inhibit NF-kappaB activation induced by various inflammatory stimuli, downregulate NF-kappaB mediated gene expression and upregulate apoptosis.