title: 5,7-Dimethoxyflavone, an activator of PPARα/γ, inhibits UVB-induced MMP expression in human skin fibroblast cells.
abstract: Peroxisome proliferator-activated receptors (PPARs), which are members of the nuclear hormone receptor superfamily, are a family of ligand-activated transcription factors that consist of three isotypes (PPAR α, δ and γ). PPAR activity was previously thought to be limited to lipid metabolism and glucose homeostasis; however, intensive studies of PPARα/γ in recent years have revealed their importance in age-related inflammation and photoaging as regulators of cytokines, matrix metalloproteinases (MMPs) and nuclear factor-kappa B (NF-κB). We evaluated the ability of the PPARα/γ activator 5,7-dimethoxyflavone (5,7-DMF) to inhibit ultraviolet B (UVB)-induced MMP expression in Hs68 human skin fibroblasts. Hs68 cells were treated with 5,7-DMF and then exposed to UVB irradiation. MMP expression, production and activity were determined by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay and gelatin zymography. PPARα/γ expression, catalase expression, and mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1) and NF-κB signalling were evaluated by Western blot analysis. PPARα/γ activity was assessed with the GAL4/PPARα/γ transactivation assay. We found that 5,7-DMF strongly decreased MMP expression, production and activity. In addition, 5,7-DMF significantly increased PPARα/γ activation and catalase expression, thereby downregulating UVB-induced reactive oxygen species (ROS) production, ROS-induced MAPK signalling and downstream transcription factors. Finally, 5,7-DMF reduced IκBα phosphorylation, blocked NF-κB p65 nuclear translocation, strongly suppressed proinflammatory cytokines such as interleukin-6 (IL-6) and IL-8. 5,7-DMF prevents UVB-induced MMP expression by suppressing UVB-induced oxidative stress and age-related inflammation via NF-κB and MAPK/AP-1 pathways. Our findings suggest the usefulness of 5,7-DMF for preventing and treating skin photoaging.
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Kim
authors.forename: Sukyeong
authors.initials: S
authors.lastname: Mun
authors.forename: Myung-Suk
authors.initials: MS
authors.lastname: Kim
authors.forename: Mi-Bo
authors.initials: MB
authors.lastname: Kim
authors.forename: Bo-Kyung
authors.initials: BK
authors.lastname: Sa
authors.forename: Jae-Kwan
authors.initials: JK
authors.lastname: Hwang
mesh_terms: D000818:Animals; D019556:COS Cells; D018929:Cell Culture Techniques; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012867:Skin / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D015595:Skin Aging / Q000187:drug effects; D014466:Ultraviolet Rays; D030521:Zingiberaceae / Q000737:chemistry
chemical_list: D005419:Flavonoids; D047493:PPAR alpha; D047495:PPAR gamma; D011837:Radiation-Protective Agents; C060298:5,7-dimethoxyflavone; D020782:Matrix Metalloproteinases