Dexamethasone attenuates methacholine-mediated aquaporin 5 downregulation in human nasal epithelial cells via suppression of NF-κB activation

Yung Lung Chang, Kai Ren Jian, Chun Shu Lin, Hsing Won Wang, Shao Cheng Liu

研究成果: 雜誌貢獻文章同行評審

3 引文 斯高帕斯(Scopus)

摘要

Background: Cholinergic stimulation plays a major role in inflammatory airway diseases. However, its role in airway surface liquid homeostasis and aquaporin 5 (AQP5) regulation remains unclear. In this study we sought to determine the effects of methacholine and dexamethasone on AQP5 expression in human nasal epithelial cells (HNEpC). Methods: HNEpC were cultured with methacholine or dexamethasone at 4 concentrations in vitro. The subcellular distribution of AQP5 was explored using immunocytochemistry. The pharmacologic effects of methacholine and dexamethasone on the expression of the phosphorylation of cyclic adenosine monophosphate–responsive element binding protein (p-CREB), AQP5, and nuclear factor-kappaB (NF-κB) were examined using Western blotting. Results: AQP5 was found to be located in cell membrane and cytoplasm and present in every group without a statistically significant difference. Methacholine inhibited expression of AQP5 and p-CREB in HNEpC, whereas dexamethasone increased these protein levels dose-dependently in a statistically significant manner. In turn, HNEpC treated with methacholine and dexamethasone showed the same trends as those intervened separately with these 2 drugs. Moreover, dexamethasone had the ability to reverse the inhibitory effect of methacholine. Western blotting revealed that, after incubation with 10−4 mol/L methacholine, NF-κB increased significantly, by 186.67%, compared with the untreated control group. Again, such an increase could be significantly reversed after dexamethasone treatment. Conclusion: NF-κB activation is important for inhibition of p-CREB/AQP5 expression after methacholine intervention, and dexamethasone adjusts it to the opposite side. This observation could provide additional insight into the anti-inflammatory effects of glucocorticoids that contribute to maintaining airway surface liquid and mucosal defense.

原文英語
頁(從 - 到)64-71
頁數8
期刊International Forum of Allergy and Rhinology
8
發行號1
DOIs
出版狀態已發佈 - 一月 2018
對外發佈

ASJC Scopus subject areas

  • 免疫學和過敏
  • 耳鼻咽喉科

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