Nano- and microplastics (NMPs), ubiquitous in the environment, pose significant health risks. We report for the first time a comprehensive study using in-vitro, in-vivo, and ex-vivo models to investigate the penetration and inflammatory effects of fragmented polystyrene (fPS) on human skin, including the analysis of both penetration depth and fPS amounts that penetrate the skin. Human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells exposed to fPS exhibited notable internalization and cytotoxicity. In a 3D human skin model, fPS particles penetrated the dermal layer within one hour, with an average maximum penetration of 4.7 μg for particles smaller than 2 µm. Similarly, mouse dorsal skin and human abdominal skin models confirmed fPS penetration. RNA sequencing revealed substantial upregulation of inflammatory genes, including IL-1α, IL-1β, IL-18, IL-6, IL-8, ICAM-1, FOS, and JUN, following fPS exposure. These findings were validated at both the mRNA and protein levels, indicating a robust inflammatory response. Notably, the inflammatory response in both the 3D human skin and mouse models increased in a dose-dependent manner, underscoring the toxicological impact of fPS on skin health. This study provides crucial insights into the mechanisms through which NMPs affect human health and underscores the need for further research to develop effective mitigation strategies.

中文翻译：

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解读联系：碎片化聚苯乙烯是皮肤炎症的驱动因素


纳米塑料和微塑料 （NMP） 在环境中无处不在，对健康构成重大风险。我们首次报告了一项使用体外、体内和体外模型的综合研究，以研究碎片聚苯乙烯 （fPS） 对人体皮肤的渗透和炎症影响，包括分析渗透深度和渗透皮肤的 fPS 量。暴露于 fPS 的人角质形成细胞 （HaCaT） 和人真皮成纤维细胞 （HDF） 细胞表现出显着的内化和细胞毒性。在 3D 人体皮肤模型中，fPS 颗粒在一小时内穿透真皮层，小于 2 μm 的颗粒平均最大穿透力为 4.7 μg。同样，小鼠背皮和人腹部皮肤模型证实了 fPS 渗透。RNA 测序显示，fPS 暴露后炎症基因显著上调，包括 IL-1α 、 IL-1β 、 IL-18 、 IL-6 、 IL-8 、 ICAM-1 、 FOS 和 JUN。这些发现在 mRNA 和蛋白质水平上都得到了验证，表明存在强烈的炎症反应。值得注意的是，3D 人类皮肤和小鼠模型中的炎症反应都以剂量依赖性方式增加，强调了 fPS 对皮肤健康的毒理学影响。这项研究为 NMP 影响人类健康的机制提供了重要见解，并强调了进一步研究以制定有效缓解策略的必要性。