Dermatological Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Campus for Ageing and Vitality, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
FASEB J. 2020 Nov;34(11):14725-14735. doi: 10.1096/fj.202001357R. Epub 2020 Sep 11.
With a large proportion of the world's population living in areas where air quality does not meet current WHO guidelines, combined with the knowledge that pollutants can interact with human skin, it is now of even greater importance that the effects of air pollutant exposure on human skin be investigated. To evaluate the damaging effects of a known component of air pollution (particulate matter) on human primary dermal fibroblasts. These studies were undertaken by exposing primary human dermal fibroblasts to different concentrations of particulate matter and analyzing the effects over time using resazurin reduction assays. Immunofluorescence microscopy was used to determine if particulate matter caused activation of the aryl hydrocarbon receptor, and phosphorylation of histone H2AX, a known marker of double-strand DNA breaks. Dot blotting was also used to analyze expression changes in secreted MMP-1, MMP-3, and TGFβ. Particulate matter was found to dose-dependently increase cellular viability, activate the aryl hydrocarbon receptor, increase double-strand DNA breaks, and increase the expression of MMP-1, MMP-3, and TGFβ. With the potential of air pollutants such as particulate matter to not only modulate the expression of proteins implicated in skin aging, but also affect cells at a genetic level, brings a pressing need for further investigation so protective strategies can be implemented.
由于世界上很大一部分人口生活在空气质量不符合世界卫生组织现行指南的地区,再加上已知污染物可以与人类皮肤相互作用,因此现在更需要研究空气污染物暴露对人类皮肤的影响。评估已知空气污染物(颗粒物)对人体原代真皮成纤维细胞的损伤作用。通过将原代人真皮成纤维细胞暴露于不同浓度的颗粒物,并使用 Resazurin 还原测定法随时间分析其影响,进行了这些研究。免疫荧光显微镜用于确定颗粒物是否导致芳烃受体的激活以及组蛋白 H2AX 的磷酸化,组蛋白 H2AX 是双链 DNA 断裂的已知标志物。斑点印迹法也用于分析分泌型 MMP-1、MMP-3 和 TGFβ 的表达变化。结果发现,颗粒物呈剂量依赖性地增加细胞活力、激活芳烃受体、增加双链 DNA 断裂,并增加 MMP-1、MMP-3 和 TGFβ 的表达。由于空气污染物(如颗粒物)不仅有可能调节与皮肤衰老相关的蛋白质的表达,而且还可能在遗传水平上影响细胞,因此迫切需要进一步研究,以便实施保护策略。