Skin damage induced by zinc oxide nanoparticles combined with UVB is mediated by activating cell pyroptosis via the NLRP3 inflammasome–autophagy–exosomal pathway

Particle and Fibre Toxicology

Yu-Hsuan Lee¹  Bour-Jr Wang²  Yu-Ying Chen³  Ying-Jan Wang⁴  Rong-Jane Chen⁵ 

[1] Department of Cosmeceutics, China Medical University, Taichung, Taiwan;Department of Cosmetic Science and Institute of Cosmetic Science, Chia Nan University of Pharmacy and Science, 71710, Tainan, Taiwan;Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, 70403, Tainan, Taiwan;Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, 70428, Tainan, Taiwan;Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, 70428, Tainan, Taiwan;Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan;Department of Food Safety/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, 70428, Tainan, Taiwan;

关键词: Zinc oxide nanoparticles;    NLRP3 inflammasomes;    Pyroptosis;    Autophagy;    Exosomes;   

DOI  :  10.1186/s12989-021-00443-w

来源: Springer

【 摘 要 】

BackgroundZinc oxide nanoparticles (ZnONPs) are widely used nanomaterial in personal cosmetics, such as skin creams and sunscreens, due to their whitening properties and strong UV light absorption. However, the safety issues and the hazards of ZnONPs, which can be taken up by the skin and cause skin toxicity, are still unclear. From a chemoprevention point of view, pterostilbene (PT) has been reported to prevent skin damage effectively by its anti-inflammatory and autophagy inducer effect. This study aims to determine the skin toxicity and the potential mechanisms of UVB and ZnONPs exposure and the preventive effect of PT.ResultsThe co-exposure of UVB and ZnONPs elicit NLRP3 inflammasome activation and pyroptosis in keratinocytes. Furthermore, exposure to both UVB and ZnONPs also disrupts cellular autophagy, which increases cell exosome release. In vivo UVB and ZnONPs exposure triggers skin toxicity, as indicated by increased histological injury, skin thickness and transepidermal water loss. Notably, the NLRP3 inflammasome-mediated pyroptosis are also activated during exposure. Topical application of pterostilbene attenuates NLRP3 inflammasome activation and pyroptosis by decreasing ROS generation and mitochondrial ROS (mtROS) levels. In addition to its antioxidant effect, PT also reversed autophagy abnormalities by restoring normal autophagic flux and decreasing NLRP3 inflammasome-loaded exosome release.ConclusionsOur findings reveal that ZnONPs induce skin damage in conjunction with UVB exposure. This process involves an interplay of inflammasomes, pyroptosis, autophagy dysfunction, and exosomes in skin toxicity. PT alleviates skin inflammation by regulating the inflammasome–autophagy–exosome pathway, a finding which could prove valuable when further evaluating ZnONPs effects for cosmetic applications.

【 授权许可】

CC BY