A nuclear factor kappa B-derived inhibitor tripeptide inhibits UVB-induced photoaging process

Abstract

Background: Ultraviolet (UV) irradiation on the skin induces photoaging which is characterized by keratinocyte hyperproliferation, generation of coarse wrinkles, worse of laxity and roughness. Upon UV irradiation, nuclear factor kappa B (NF-kappa B) is activated which plays a key role in signaling pathway leading to inflammation cascade and this activation stimulates expression of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin-1alpha (IL-1 alpha) and a stress response gene cyclooxygenase-2 (COX-2). In addition, activation of NF-kappa B up-regulates the expression of matrix metalloprotease-1 (MMP-1) and consequently collagen in dermis is degraded. Objective: In this study, the effects of a NF-kappa B-derived inhibitor tripeptide on the UVB-induced photoaging and inflammation were investigated in vitro and in vivo. Methods: A NF-kappa B-derived inhibitor tripeptide (NF-kappa B-DVH) was synthesized based on the sequence of dimerization region of the subunit p65 of NF-kappa B. Its inhibitory activity was confirmed using chromatin immunoprecipitation assay and in situ proximate ligation assay. The effects of anti-photoaging and anti-inflammation were analyzed by Enzyme-linked immunosorbent assay (ELISA), immunoblotting and immunochemistry. Results: NF-kappa B-DVH significantly decreased UV-induced expression of TNF-alpha, IL-1 alpha, MMP-1 and COX-2 while increased production of type I procollagen. Conclusion: Results showed NF-kappa B-DVH had strong anti-inflammatory activity probably by inhibiting NF-kappa B activation pathway and suggested to be used as a novel agent for anti-photoaging. (C) 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.