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丙烯基异硫氰酸酯通过上调紧密连接蛋白和 TRPA1 调制缓解屋尘螨诱导的变应性哮喘模型中的气道炎症和收缩。

Allyl isothiocyanate mitigates airway inflammation and constriction in a house dust mite-induced allergic asthma model via upregulation of tight junction proteins and the TRPA1 modulation.

机构信息

School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.

Deaprtment of Obstertrics and Gynecology, University of Chicago, 60637 Chicago, IL, USA; Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, 11566 Cairo, Egypt.

出版信息

Biomed Pharmacother. 2023 Oct;166:115334. doi: 10.1016/j.biopha.2023.115334. Epub 2023 Aug 25.

Abstract

Asthma is a chronic inflammatory disease that has been associated with insufficient vegetable intake. Allyl Isothiocyanate (AITC) is a natural isothiocyanate found in cruciferous plants with anti-inflammatory and antioxidant abilities. Our study aimed to investigate the potential effect of AITC on tracheal constriction in a house dust mite (HDM)-induced asthma animal model, and explore the underlying mechanisms. To investigate the effects of AITC on HDM-induced allergic asthma model, established by intranasally administering extracts of HDM and AITC or DEX was given orally for four weeks. Flexivent SCIREQ, H&E staining, ELISA were employed to evaluate the lung function and the cytokine secretion. Possible mechanisms were determined by Western blot. Rat tracheae contraction was measured by Labscribe. We utilized lung epithelial cells (BEAS-2B) to assess the adhesion response to the combination of inflammatory factors TNF-α and IL-4. The results of the study showed that AITC significantly reduced tracheal constriction in ex vivo experiments and improved lung function in in vivo experiments compared to HDM-induced mice. Additionally, AITC decreased cytokine secretion, inflammatory cell infiltration in the lung, and constriction-related proteins expression in both lung and tracheae. Moreover, AITC increased tight junction-related protein expression in lung tissues. In vitro experiments showed that AITC had a protective effect through TRPA1 channel without affecting cell viability. Our results demonstrate that AITC has potential anti-asthma effects in HDM-induced asthma models by alleviating airway inflammation and airway constriction through increasing tight junction-related protein expression and suppressing Ca signaling. These findings suggest that AITC may be a beneficial adjuvant therapy in asthma treatment.

摘要

哮喘是一种慢性炎症性疾病,与蔬菜摄入不足有关。丙烯基异硫氰酸酯(AITC)是十字花科植物中发现的一种天然异硫氰酸酯,具有抗炎和抗氧化作用。我们的研究旨在探讨 AITC 对屋尘螨(HDM)诱导的哮喘动物模型中气管收缩的潜在影响,并探讨其潜在机制。为了研究 AITC 对 HDM 诱导的变应性哮喘模型的影响,通过鼻腔给予 HDM 提取物和 AITC 或 DEX 进行口服给药,共给药 4 周。采用 Flexivent SCIREQ、H&E 染色、ELISA 评估肺功能和细胞因子分泌。通过 Western blot 确定可能的机制。通过 Labscribe 测量大鼠气管收缩。我们利用肺上皮细胞(BEAS-2B)评估炎性因子 TNF-α和 IL-4 组合对细胞黏附的反应。研究结果表明,与 HDM 诱导的小鼠相比,AITC 显著减少了离体实验中的气管收缩,并改善了体内实验中的肺功能。此外,AITC 降低了细胞因子分泌、肺部炎症细胞浸润以及肺和气管中与收缩相关的蛋白表达。此外,AITC 增加了肺组织中紧密连接相关蛋白的表达。体外实验表明,AITC 通过 TRPA1 通道发挥保护作用,而不影响细胞活力。我们的研究结果表明,AITC 通过增加紧密连接相关蛋白的表达和抑制 Ca 信号,对 HDM 诱导的哮喘模型具有潜在的抗哮喘作用,从而减轻气道炎症和气道收缩。这些发现表明,AITC 可能是哮喘治疗的有益辅助治疗方法。

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