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TFEB and TFE3 cooperate in regulating inorganic arsenic-induced autophagy-lysosome impairment and immuno-dysfunction in primary dendritic cells.
Xu, Guowei; Peng, Huaguang; Yao, Ran; Yang, Yuqing; Li, Bing.
Afiliación
  • Xu G; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education (China Medical University), Shenyang, Liaoning, People's Republic of China.
  • Peng H; Environment and Non-Communicable Disease Research Center, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area Liaoning Province, Shenyang, 110122, People's
  • Yao R; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education (China Medical University), Shenyang, Liaoning, People's Republic of China.
  • Yang Y; Environment and Non-Communicable Disease Research Center, Key Laboratory of Arsenic-Related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area Liaoning Province, Shenyang, 110122, People's
  • Li B; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education (China Medical University), Shenyang, Liaoning, People's Republic of China.
Cell Biol Toxicol ; 40(1): 4, 2024 01 25.
Article en En | MEDLINE | ID: mdl-38267572
ABSTRACT
Arsenic (As) is a prevalent and hazardous environmental toxicant associated with cancer and various health problems, which has been shown suppressive effects on dendritic cells (DCs). Autophagy is essential for the innate and adaptive immune responses of DCs, and the transcription factors TFEB and TFE3 are key regulators of autophagic and lysosomal target genes. However, the detrimental alterations of the autophagy-lysosome pathway in As-exposed DCs and the possible coordinating roles of TFEB and TFE3 in the immune dysfunction of this cell are less understood. In this paper, we found that As exposure significantly impaired lysosomal number, lysosomal acidic environment, and lysosomal membrane permeabilization, which might lead to blocked autophagic flux in cultured DCs. Furthermore, our results confirmed that TFEB or TFE3 knockdown exacerbated the disorders of lysosome and the blockade of autophagic flux in As-exposed DCs, and also enhanced the inhibitory expression of co-stimulatory molecules Cd80 and Cd83; adhesion molecule Icam1; cytokines TNF-α, IL-1ß, and IL-6; chemokine receptor Ccr7; and antigen-presenting molecules MHC II and MHC I. By contrast, overexpression of TFEB or TFE3 partially alleviated the above-mentioned impairment of DCs by inorganic As exposure. In conclusion, these findings reveal a previously unappreciated inhibition of lysosome-mediated degradation and damage of lysosomal membrane integrity leading to dysregulated autophagy and impaired immune functions of DCs by arsenicals, and also suggest TFEB and TFE3 as potential therapeutic targets for ameliorating As toxicity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arsénico / Arsenicales Idioma: En Revista: Cell Biol Toxicol Asunto de la revista: TOXICOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arsénico / Arsenicales Idioma: En Revista: Cell Biol Toxicol Asunto de la revista: TOXICOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Suiza