1142 The IL-1α stimulated expression of the wrinkle-inducing elastase neprilysin in adult human dermal fibroblasts is mediated via an intracellular signaling axis of ERK/JNK/c-Jun/c-Fos/AP-1

Neprilysin (NPL) is a wrinkle-inducing membrane bound elastase that expressed abundantly in UV-exposed and aged dermal fibroblasts (JBC2010). The overexpression of NPL essentially associated with enhanced epithelial-mesenchymal cytokine interactions (EMCI) mainly via IL-1α which has distinct potential to stimulate the expression by human (HDFs)(BJ2012). over-expression also accelerates wrinkle formation, accompanied disruptions three-dimensional architecture elastic fibers responsible for loss skin elasticity (JID 2001). Because signaling pathways leading IL-1a-stimulated HDFs remain unclear, we characterized pathway involved, including its transcription factor, IL-1a-treated HDFs. Since qRT-PCR analysis revealed mRNA level stimulated stronger extent adult (HDFa) IL-1a than neonatal HDFs, used HDFa analysis. Western blotting phosphorylation factors significantly ERK1/2, JNK, p38, MSK1, NFkB, c-Jun, ATF2 STAT3. Analysis using inhibitors demonstrated ERK JNK but not NFkB or STAT3 abrogated at mRNA, protein activity levels. Furthermore, c-Fos silencing downregulated IL-1α-increased These findings strongly suggest IL-1α-stimulated mediated an intracellular axis ERK/JNK/c-Jun/c-Fos/AP-1.