title: Diphlorethohydroxycarmalol Suppresses Ultraviolet B-Induced Matrix Metalloproteinases via Inhibition of JNK and ERK Signaling in Human Keratinocytes.
abstract: Skin aging is the most readily observable process involved in human aging. Ultraviolet B (UVB) radiation causes photo-oxidation via generation of reactive oxygen species (ROS), thereby damaging the nucleus and cytoplasm of skin cells and ultimately leading to cell death. Recent studies have shown that high levels of solar UVB irradiation induce the synthesis of matrix metalloproteinases (MMPs) in skin fibroblasts, causing photo-aging and tumor progression. The MMP family is involved in the breakdown of extracellular matrix in normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as arthritis and metastasis. We investigated the effect of diphlorethohydroxycarmalol (DPHC) against damage induced by UVB radiation in human skin keratinocytes. In UVB-irradiated cells, DPHC significantly reduced expression of MMP mRNA and protein, as well as activation of MMPs. Furthermore, DPHC reduced phosphorylation of ERK and JNK, which act upstream of c-Fos and c-Jun, respectively; consequently, DPHC inhibited the expression of c-Fos and c-Jun, which are key components of activator protein-1 (AP-1, up-regulator of MMPs). Additionally, DPHC abolished the DNA-binding activity of AP-1, and thereby prevented AP-1-mediated transcriptional activation. These data demonstrate that by inactivating ERK and JNK, DPHC inhibits induction of MMPs triggered by UVB radiation.
authors.affiliation: School of Medicine, College of Natural Sciences, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.affiliation: School of Medicine, College of Natural Sciences, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Madduma Hewage
authors.initials: MH
authors.lastname: Susara Ruwan Kumara
authors.affiliation: School of Medicine, College of Natural Sciences, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Ki Cheon
authors.initials: KC
authors.lastname: Kim
authors.affiliation: School of Medicine, College of Natural Sciences, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.affiliation: School of Medicine, College of Natural Sciences, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Kang
authors.affiliation: Department of Chemistry, College of Natural Sciences, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Nam Ho
authors.initials: NH
authors.lastname: Lee
authors.affiliation: School of Medicine, College of Natural Sciences, Jeju National University, Jeju 63243, Republic of Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
keywords: Diphlorethohydroxycarmalol; Human skin keratinocytes; Matrix metalloproteinases; Photo-aging; Ultraviolet B