Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
School of Science, Monash University Malaysia, Subang Jaya, Malaysia.
Immunopharmacol Immunotoxicol. 2021 Dec;43(6):813-824. doi: 10.1080/08923973.2021.1992633. Epub 2021 Oct 25.
The airway epithelial barrier can be disrupted by house dust mite (HDM) allergens leading to allergic airway inflammation. Zerumbone, a natural monocyclic sesquiterpene, was previously found to possess anti-asthmatic effect by modulating Th1/Th2 cytokines. However, the protective role of zerumbone on epithelial barrier function remains to be fully explored.
To investigate the effect of zerumbone on HDM extract-induced airway epithelial barrier dysfunction.
Human bronchial epithelial cells 16HBE14o- were incubated with 100 μg/mL HDM extract and treated with non-cytotoxic concentrations of zerumbone (6.25 μM, 12.5 μM, and 25 μM) for 24 h. The epithelial junctional integrity and permeability were evaluated through transepithelial electrical resistance (TEER) and fluorescein isothiocynate (FITC)-Dextran permeability assays, respectively. The localization of junctional proteins, occludin and zona occludens (ZO)-1, was studied using immunofluorescence (IF) while the protein expression was measured by western blot.
Zerumbone inhibited changes in junctional integrity (6.25 μM, ≤ .05; 12.5 μM, ≤ .001; 25 μM, ≤ .001) and permeability (6.25 μM, ≤ .05; 12.5 μM, ≤ .01; 25 μM, ≤ .001) triggered by HDM extract in a concentration-dependent manner. This protective effect could be explained by the preservation of occludin (12.5 μM, ≤ .01 and 25 μM, ≤ .001) and ZO-1 (12.5 μM, ≤ .05 and 25 μM, ≤ .001) localization, rather than the prevention of their cleavage.
Zerumbone attenuates HDM extract-induced epithelial barrier dysfunction which supports its potential application for the treatment of inflammation-driven airway diseases such as asthma.
屋尘螨（HDM）过敏原可破坏气道上皮屏障，导致过敏性气道炎症。此前的研究发现，姜烯具有通过调节 Th1/Th2 细胞因子发挥抗哮喘作用。然而，姜烯对上皮屏障功能的保护作用仍有待充分探索。
研究姜烯对 HDM 提取物诱导的气道上皮屏障功能障碍的影响。
将人支气管上皮细胞 16HBE14o-与 100μg/mL HDM 提取物孵育，并使用非细胞毒性浓度的姜烯（6.25μM、12.5μM 和 25μM）处理 24 小时。通过跨上皮电阻（TEER）和荧光素异硫氰酸酯（FITC）-右旋糖酐通透性测定分别评估上皮连接完整性和通透性。使用免疫荧光（IF）研究连接蛋白紧密连接蛋白（occludin）和封闭蛋白（ZO）-1 的定位，并用 Western blot 测量蛋白表达。
姜烯抑制了由 HDM 提取物引起的连接完整性（6.25μM，≤.05；12.5μM，≤.001；25μM，≤.001）和通透性（6.25μM，≤.05；12.5μM，≤.01；25μM，≤.001）的变化，呈浓度依赖性。这种保护作用可以通过 occludin（12.5μM，≤.01 和 25μM，≤.001）和 ZO-1（12.5μM，≤.05 和 25μM，≤.001）的定位得以解释，而不是防止其裂解。
姜烯可减轻 HDM 提取物诱导的上皮屏障功能障碍，支持其在治疗哮喘等炎症驱动的气道疾病中的潜在应用。
