https://scholars.lib.ntu.edu.tw/handle/123456789/594001
標題: | Vitamin D3 decreases TNF-α-induced inflammation in lung epithelial cells through a reduction in mitochondrial fission and mitophagy | 作者: | Chen, Yu-Chen Sung, Hsin-Ching Chuang, Tzu-Yi Lai, Tsai-Chun Lee, Tzu-Lin Lee, Chiang-Wen Lee, I-Ta YUH-LIEN CHEN |
關鍵字: | Adhesion molecules; Inflammation; Mitochondrial fission; Mitophagy; ROS; Vitamin D3 | 公開日期: | 13-七月-2021 | 出版社: | SPRINGER | 來源出版物: | Cell biology and toxicology | 摘要: | Previous work has shown an association between vitamin D3 deficiency and an increased risk for acquiring various inflammatory diseases. Vitamin D3 can reduce morbidity and mortality in these patients via different mechanisms. Lung inflammation is an important event in the initiation and development of respiratory disorders. However, the anti-inflammatory effects of vitamin D3 and the underlying mechanisms remained to be determined. The purpose of this study was to examine the effects and mechanisms of action of vitamin D3 (Vit. D) on the expression of intercellular adhesion molecule-1 (ICAM-1) in vitro and in vivo with or without tumor necrosis factor α (TNF-α) treatment. Pretreatment with Vit. D reduced the expression of ICAM-1 and leukocyte adhesion in TNF-α-treated A549 cells. TNF-α increased the accumulation of mitochondrial reactive oxygen species (mtROS), while Vit. D reduced this effect. Pretreatment with Vit. D attenuated TNF-α-induced mitochondrial fission, as shown by the increased expression of mitochondrial fission factor (Mff), phosphorylated dynamin-related protein 1 (p-DRP1), and mitophagy-related proteins (BCL2/adenovirus E1B 19 kDa protein-interacting protein 3, Bnip3) in A549 cells. Inhibition of DRP1 or Mff significantly decreased ICAM-1 expression. In addition, we found that Vit. D decreased TNF-α-induced ICAM-1 expression, mitochondrial fission, and mitophagy via the AKT and NF-κB pathways. Moreover, ICAM-1 expression, mitochondrial fission, and mitophagy were increased in the lung tissues of TNF-α-treated mice, while Vit. D supplementation reduced these effects. In this study, we elucidated the mechanisms by which Vit. D reduces the expression of adhesion molecules in models of airway inflammation. Vit. D might be served as a novel therapeutic agent for the targeting of epithelial activation in lung inflammation. Graphical Headlights: • The expression of DRP1 and Mff, mitochondrial fission-related proteins, was increased in TNF-α-treated A549 cells. • The expression of Bnip3 and LC3B, mitophagy-related proteins, was increased in TNF-α-treated A549 cells. • Vit. D pretreatment decreased TNF-α-induced inflammation through the reduction of mitochondrial fission and mitophagy in A549 cells. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/594001 | ISSN: | 0742-2091 | DOI: | 10.1007/s10565-021-09629-6 |
顯示於: | 解剖學暨細胞生物學科所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。