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5,7‐Dimethoxyflavone, an activator of PPARα/γ, inhibits UVB‐induced MMP expression in human skin fibroblast cells
Author(s) -
Kim Jae Kyung,
Mun Sukyeong,
Kim MyungSuk,
Kim MiBo,
Sa BoKyung,
Hwang JaeKwan
Publication year - 2012
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2011.01435.x
Subject(s) - fibroblast , human skin , activator (genetics) , dermal fibroblast , matrix metalloproteinase , chemistry , peroxisome proliferator activated receptor , microbiology and biotechnology , skin aging , cancer research , medicine , biology , dermatology , receptor , biochemistry , in vitro , genetics
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.