Cellular response of keratinocytes to the entry and accumulation of nanoplastic particles

Journal Article · 29 April 2024 · Particle and Fibre Toxicology

DOI: https://doi.org/10.1186/s12989-024-00583-9 · OSTI ID:2438505

Martin, Leisha ^[1]; Simpson, Kayla ^[1]; Brzezinski, Molly ^[1]; Watt, John Daniel  ^[2]; Xu, Wei ^[1]

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1. Texas A & M Univ., Corpus Christi, TX (United States)
2. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States). Center for Integrated Nanotechnologies (CINT)

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.

• Research Organization: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
• Sponsoring Organization: USDOE Office of Science (SC). Office of Basic Energy Sciences (BES)
• Grant/Contract Number: 89233218CNA000001
• OSTI ID: 2438505
• Report Number(s): LA-UR--23-25636
• Journal Information: Particle and Fibre Toxicology, Journal Name: Particle and Fibre Toxicology Journal Issue: 1 Vol. 21; ISSN 1743-8977
• Publisher: BioMed CentralCopyright Statement
• Country of Publication: United States
• Language: English