Nuclear factor kappa B (NF-B), a transcription factor found in almost every cell types, is known to regulate the expression of various inflammatory cytokines and cellular processes such as immune-mediated and inflammatory response, cellular growth and apoptosis. It is constantly active in a variety of diseases including inflammatory diseases. Caffeic acid phenethyl ester (CAPE), a natural polyphenolic compound, is known to inhibit the activation of NF-B and attenuate inflammation during various inflammatory conditions, but its function during autoimmune inflammatory disorders is largely obscure. Therefore, herein we investigated the therapeutic potential of CAPE and its derivatives to inhibit the translocation of NF-B from cytoplasm into nucleus. We first examined toxic effects of CAPE and its derivatives using mouse inflammatory macrophage cell line (RAW 264.7). No toxicity was observed up to 6 hr incubation at 50 -100 µM concentration for all compounds tested. After 24 hr incubation, CAPE and its derivatives showed different cytotoxicity profiles. Only nontoxic dose of CAPE and its derivatives is used for further studies. Because activation of NF-B requires degradation of an inhibitory protein IBα, we evaluated the effect of CAPE on maintenance of IBα integrity. CAPE at 50 µM prevented IBα degradation induced by NF-B activator betulinic acid. Further, we are in the process evaluating the effects of CAPE derivatives on prevention of IBα degradation when compared to parental CAPE molecule. Thus, our preliminary studies suggest that identification of potential inhibitor of NF-B activation with less cytotoxicity could be a novel therapeutic strategy to attenuate immune-complex mediated inflammatory disorders.
Available at: http://works.bepress.com/xinyu_wang/2/