Department of Life Sciences, College of Science, Texas A&M University - Corpus Christi, 6300 Ocean Dr, 78412, Corpus Christi, TX, USA.
Center for Integrated Nanotechnologies, Los Alamos National Laboratory, Albuquerque, NM, USA.
Part Fibre Toxicol. 2024 Apr 29;21(1):22. doi: 10.1186/s12989-024-00583-9.
Plastic accumulation in the environment is rapidly increasing, and nanoplastics (NP), byproducts of environmental weathering of bulk plastic waste, pose a significant public health risk. Particles may enter the human body through many possible routes such as ingestion, inhalation, and skin absorption. However, studies on NP penetration and accumulation in human skin are limited. Loss or reduction of the keratinized skin barrier may enhance the skin penetration of NPs. The present study investigated the entry of NPs into a human skin system modeling skin with compromised barrier functions and cellular responses to the intracellular accumulations of NPs. Two in vitro models were employed to simulate human skin lacking keratinized barriers. The first model was an ex vivo human skin culture with the keratinized dermal layer (stratum corneum) removed. The second model was a 3D keratinocyte/dermal fibroblast cell co-culture model with stratified keratinocytes on the top and a monolayer of skin fibroblast cells co-cultured at the bottom. The penetration and accumulation of the NPs in different cell types were observed using fluorescent microscopy, confocal microscopy, and cryogenic electron microscopy (cryo-EM). The cellular responses of keratinocytes and dermal fibroblast cells to stress induced by NPs stress were measured. The genetic regulatory pathway of keratinocytes to the intracellular NPs was identified using transcript analyses and KEGG pathway analysis. The cellular uptake of NPs by skin cells was confirmed by imaging analyses. Transepidermal transport and penetration of NPs through the skin epidermis were observed. According to the gene expression and pathway analyses, an IL-17 signaling pathway was identified as the trigger for cellular responses to internal NP accumulation in the keratinocytes. The transepidermal NPs were also found in co-cultured dermal fibroblast cells and resulted in a large-scale transition from fibroblast cells to myofibroblast cells with enhanced production of α-smooth muscle actin and pro-Collagen Ia. The upregulation of inflammatory factors and cell activation may result in skin inflammation and ultimately trigger immune responses.
环境中塑料的积累正在迅速增加，而纳米塑料（NP）是大块塑料废物环境风化的副产品，对公共健康构成了重大威胁。颗粒可能通过多种途径进入人体，如摄入、吸入和皮肤吸收。然而，关于 NP 穿透和在人体皮肤中积累的研究有限。角质化皮肤屏障的丧失或减少可能会增强 NP 的皮肤穿透性。本研究调查了 NP 进入具有受损屏障功能的人体皮肤系统的情况，以及细胞对 NP 细胞内积累的反应。采用两种体外模型模拟缺乏角质化屏障的人体皮肤。第一种模型是去除角质化真皮层（角质层）的离体人皮肤培养物。第二种模型是 3D 角质形成细胞/真皮成纤维细胞共培养模型，顶部有分层的角质形成细胞，底部有单层皮肤成纤维细胞共培养。使用荧光显微镜、共聚焦显微镜和低温电子显微镜（cryo-EM）观察 NP 在不同细胞类型中的穿透和积累。测量角质形成细胞和真皮成纤维细胞对 NP 应激诱导的细胞应激的反应。使用转录分析和 KEGG 途径分析鉴定角质形成细胞对细胞内 NP 的遗传调节途径。通过成像分析证实了皮肤细胞对 NP 的细胞摄取。观察了 NP 通过皮肤表皮的经皮转运和穿透。根据基因表达和途径分析，鉴定出白细胞介素 17（IL-17）信号通路是角质形成细胞对细胞内 NP 积累的细胞反应的触发因素。还在共培养的真皮成纤维细胞中发现了经皮 NP，并导致成纤维细胞向肌成纤维细胞的大规模转变，α-平滑肌肌动蛋白和前胶原蛋白 Ia 的产生增加。炎症因子和细胞激活的上调可能导致皮肤炎症，并最终引发免疫反应。
