title: Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts.
abstract: Ultraviolet (UV) irradiation regulates UV-responsive genes, including matrix metalloproteinases (MMPs). Moreover, UV-induced MMPs cause connective tissue damage and the skin to become wrinkled and aged. Here, we investigated the effect of eicosapentaenoic acid (EPA), a dietary omega-3 fatty acid, on UV-induced MMP-1 expression in human dermal fibroblasts (HDFs). We found that UV radiation increases MMP-1 expression and that this is mediated by p44 and p42 MAP kinase (ERK) and Jun-N-terminal kinase (JNK) activation but not by p38 activation. Pretreatment of HDFs with EPA inhibited UV-induced MMP-1 expression in a dose-dependent manner and also inhibited the UV-induced activation of ERK and JNK by inhibiting ERK kinase (MEK1) and SAPK/ERK kinase 1 (SEK1) activation, respectively. Moreover, inhibition of ERK and JNK by EPA resulted in the decrease of c-Fos expression and c-Jun phosphorylation/expression induced by UV, respectively, which led to the inhibition of UV-induced activator protein-1 DNA binding activity. This inhibitory effect of EPA on MMP-1 was not mediated by an antioxidant effect. We also found that EPA inhibited 12-O-tetradecanoylphorbol-13-acetate- or tumor necrosis factor-alpha-induced MMP-1 expression in HDFs and UV-induced MMP-1 expression in HaCaT cells. In conclusion, our results demonstrate that EPA can inhibit UV-induced MMP-1 expression by inhibiting the MEK1/ERK/c-Fos and SEK1/JNK/c-Jun pathways. Therefore, EPA is a potential agent for the prevention and treatment of skin aging.
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyeon Ho
authors.initials: HH
authors.lastname: Kim
authors.forename: Chung Min
authors.initials: CM
authors.lastname: Shin
authors.forename: Chi-Hyun
authors.initials: CH
authors.lastname: Park
authors.forename: Kyu Han
authors.initials: KH
authors.lastname: Kim
authors.forename: Kwang Hyun
authors.initials: KH
authors.lastname: Cho
authors.forename: Hee Chul
authors.initials: HC
authors.lastname: Eun
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Chung
mesh_terms: D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000166:cytology; D014466:Ultraviolet Rays
chemical_list: D015525:Fatty Acids, Omega-3; D015118:Eicosapentaenoic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020781:Matrix Metalloproteinase 1