SELECTIVE INHIBITORS OF NUCLEAR FACTOR-KB ACTIVATION AND USES THEREOF

摘要

The present invention provides cell permeable NF-kB inhibitors consist of a polypeptide derived from the p65 subunit of NF-kB and a protein transduction domain derived from antennapedia third helix sequence. The inhibitor suppressed NF-kB activation induced by TNF, LPS, IL-1, okadaic acid, PMA, H2O2 and cigarette smoke condensate. NF-kB-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-kB inhibitor that can selectively inhibit NF-kB activation induced by various inflammatory stimuli, downregulate NFkB mediated gene expression and upregulate apoptosis.