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 abstract

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.

中文翻译：

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维生素 D3 通过减少线粒体裂变和线粒体自噬来减少 TNF-α 诱导的肺上皮细胞炎症

先前的研究表明，维生素 D ₃缺乏症与患各种炎症性疾病的风险增加之间存在关联。维生素 D ₃可以通过不同的机制降低这些患者的发病率和死亡率。肺部炎症是呼吸系统疾病发生和发展的重要事件。_{然而，维生素 D 3}的抗炎作用及其潜在机制仍有待确定。_{本研究的目的是检查维生素 D 3}的作用和作用机制(Vit. D) 在有或没有肿瘤坏死因子 α (TNF-α) 治疗的情况下体外和体内细胞间粘附分子 1 (ICAM-1) 的表达。用维生素预处理。D 降低了 TNF-α 处理的 A549 细胞中 ICAM-1 的表达和白细胞粘附。TNF-α 增加了线粒体活性氧 (mtROS) 的积累，而 Vit。D 减少了这种影响。用维生素预处理。D 减弱 TNF-α 诱导的线粒体裂变，如线粒体裂变因子 (Mff)、磷酸化动力相关蛋白 1 (p-DRP1) 和线粒体自噬相关蛋白 (BCL2/腺病毒 E1B 19 kDa 蛋白- A549 细胞中的相互作用蛋白 3，Bnip3)。DRP1 或 Mff 的抑制显着降低了 ICAM-1 的表达。此外，我们还发现了 Vit. D 降低 TNF-α 诱导的 ICAM-1 表达，通过 AKT 和 NF-κB 途径进行线粒体分裂和线粒体自噬。此外，ICAM-1 表达、线粒体裂变和线粒体自噬在 TNF-α 处理的小鼠的肺组织中增加，而 Vit. D 补充剂减少了这些影响。在这项研究中，我们阐明了 Vit. D 降低气道炎症模型中粘附分子的表达。维生素。D 可能用作靶向肺部炎症上皮活化的新型治疗剂。D 降低气道炎症模型中粘附分子的表达。维生素。D 可能用作靶向肺部炎症上皮活化的新型治疗剂。D 降低气道炎症模型中粘附分子的表达。维生素。D 可能用作靶向肺部炎症上皮活化的新型治疗剂。

图形概要

图形大灯：

• DRP1 和 Mff（线粒体裂变相关蛋白）的表达在 TNF-α 处理的 A549 细胞中增加。

• Bnip3 和 LC3B（线粒体自噬相关蛋白）的表达在 TNF-α 处理的 A549 细胞中增加。

• 维生素。D 预处理通过减少 A549 细胞中的线粒体裂变和线粒体自噬来减少 TNF-α 诱导的炎症。