1. Academic Validation
  2. ZnO nanoparticles induce melanoma-like lesions via recruiting dermal dendritic cells in barrier-damaged skin in mice

ZnO nanoparticles induce melanoma-like lesions via recruiting dermal dendritic cells in barrier-damaged skin in mice

  • Food Chem Toxicol. 2024 Aug 26:193:114948. doi: 10.1016/j.fct.2024.114948.
Menghan You 1 Yingying Huang 2 Yeda Chen 3 Dan Li 4 Yaping Tang 4 Yi Kuan Du 5 Hong Yang 6 Anfa Liang 3 Guodong Hu 7 Yinghua Chen 8
Affiliations

Affiliations

  • 1 Dongguan People's Hospital Biobank, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Guangzhou, Guangdong, 510515, China.
  • 2 Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue, Guangzhou, Guangdong, 510515, China.
  • 3 Dongguan People's Hospital Biobank, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China.
  • 4 Department of Dermatology, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China; Dongguan Key Laboratory of Translational Medicine in Skin and Immune Diseases, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China.
  • 5 Dongguan People's Hospital Central Laboratory, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China.
  • 6 Department of Respiratory and Critical Care Medicine, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China.
  • 7 Department of Respiratory and Critical Care Medicine, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China. Electronic address: huguodong@smu.edu.cn.
  • 8 Dongguan People's Hospital Biobank, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Sciences, Guangzhou, Guangdong, 510515, China; Dongguan Key Laboratory of Translational Medicine in Skin and Immune Diseases, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, 523059, China. Electronic address: mrchch@126.com.
Abstract

ZnO nanoparticles (NPs) are used in skin treatments and cosmetics, the toxicity of long-term and continuous exposure to ZnO NPs is unknown. Mice with epidermal barrier dysfunction revealed melanoma-like lesions after continuous exposure to ZnO NPs. However, the effects of metallic NPs on the skin microenvironment and immune system remain poorly understood. Mice with epidermal barrier failure were given continuous exposure to ZnO NPs for 7 weeks. The malignant transformation of melanocytes was induced with ZnO NPs 2.5 μg/ml for 72 h exposure. The supernatant of the culture medium from dendritic cells after being exposed to 10 μg/ml ZnO NPs for 24 h was applied to melanocytes to explore the effect of recruitment of DCs. The expressure of ZnO NPs resulted in a tendency of malignant transformation of melanocytes, the recruitment of DCs induces this process by produce inflammatory factors such as TNF-α. These DC-produced inflammatory factors, which were induced by ZnO NP exposure, increased the production of Matrix Metalloproteinases in melanocytes and expedited the malignant transformation process. Our findings revealed that the disrupted cutaneous microenvironment by ZnO NPs penetrated directly promoted the malignant transformation of melanocytes, which process also indirectly enhanced by the TNF-αsecreted from the recruited DCs.

Keywords

Dendritic cells; MMPs; Malignant transformation; Melanocyte; TNF-α; Zinc oxide nanoparticles.

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