title: Biological mechanisms underlying the ultraviolet radiation-induced formation of skin wrinkling and sagging II: over-expression of neprilysin plays an essential role.
abstract: Our previous studies strongly indicated that the up-regulated activity of skin fibroblast-derived elastase plays a pivotal role in wrinkling and/or sagging of the skin via the impairment of elastic fiber configuration and the subsequent loss of skin elasticity. Fortunately, we succeeded in identifying human skin fibroblast-derived elastase as a previously known enzyme, neprilysin or neutral endopeptidase (NEP). We have also characterized epithelial-mesenchymal paracrine cytokine interactions between UVB-exposed-keratinocytes and dermal fibroblasts and found that interleukin-1α and granulocyte macrophage colony stimulatory factor (GM-CSF) are intrinsic cytokines secreted by UVB-exposed keratinocytes that stimulate the expression of neprilysin by fibroblasts. On the other hand, direct UVA exposure of human fibroblasts significantly stimulates the secretion of IL-6 and also elicits a significant increase in the gene expression of matrix metallo-protease(MMP)-1 as well as neprilysin (to a lesser extent), which is followed by distinct increases in their protein and enzymatic activity levels. Direct UVA exposure of human keratinocytes also stimulates the secretion of IL-6, IL-8 and GM-CSF but not of IL-1 and endothelin-1. These findings suggest that GM-CSF secreted by UVA-exposed keratinocytes as well as IL-6 secreted by UVA-exposed dermal fibroblasts play important and additional roles in UVA-induced sagging and wrinkling by up-regulation of neprilysin and MMP-1, respectively, in dermal fibroblasts.
authors: Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan. imokawag@dream.ocn.ne.jp.
authors: Genji
authors: G
authors: Imokawa
authors: School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan. ozzy_ozzy41@yahoo.co.jp.
authors: Hiroaki
authors: H
authors: Nakajima
authors: Skin Care Products Research, Kao Corporation, Tokyo 131-8501, Japan. ishida.koichi@kao.co.jp.
authors: Koichi
authors: K
authors: Ishida
mesh_terms: D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D015260:Neprilysin / Q000235:genetics*; D012867:Skin / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D015595:Skin Aging / Q000235:genetics / Q000473:pathology* / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015260:Neprilysin