Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Exp Dermatol. 2012 Mar;21(3):211-6. doi: 10.1111/j.1600-0625.2011.01435.x.
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.
过氧化物酶体增殖物激活受体 (PPARs) 是核激素受体超家族的成员，是一组配体激活的转录因子，由三种同工型 (PPARα、δ 和γ) 组成。PPAR 活性以前被认为仅限于脂质代谢和葡萄糖稳态；然而，近年来对 PPARα/γ 的深入研究揭示了它们作为细胞因子、基质金属蛋白酶 (MMPs) 和核因子-κB (NF-κB) 的调节剂在与年龄相关的炎症和光老化中的重要性。我们评估了 PPARα/γ 激活剂 5,7-二甲氧基黄酮 (5,7-DMF) 抑制人皮肤成纤维细胞 Hs68 中紫外线 B (UVB) 诱导的 MMP 表达的能力。用 5,7-DMF 处理 Hs68 细胞，然后暴露于 UVB 照射下。通过逆转录聚合酶链反应、酶联免疫吸附测定和明胶酶谱法测定 MMP 表达、产生和活性。通过 Western blot 分析评估 PPARα/γ 表达、过氧化氢酶表达以及丝裂原活化蛋白激酶 (MAPK)、激活蛋白-1 (AP-1) 和 NF-κB 信号。用 GAL4/PPARα/γ 转录激活测定评估 PPARα/γ 活性。我们发现 5,7-DMF 强烈降低 MMP 表达、产生和活性。此外，5,7-DMF 显著增加 PPARα/γ 激活和过氧化氢酶表达，从而下调 UVB 诱导的活性氧 (ROS) 产生、ROS 诱导的 MAPK 信号和下游转录因子。最后，5,7-DMF 减少 IκBα 磷酸化，阻断 NF-κB p65 核易位，强烈抑制白细胞介素-6 (IL-6) 和 IL-8 等促炎细胞因子。5,7-DMF 通过抑制 NF-κB 和 MAPK/AP-1 途径抑制 UVB 诱导的氧化应激和与年龄相关的炎症，从而防止 UVB 诱导的 MMP 表达。我们的研究结果表明，5,7-DMF 可用于预防和治疗皮肤光老化。
