Department of Immunology, University of Manitoba, Winnipeg, MB, Canada.
Manitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
Cytokine. 2023 Dec;172:156414. doi: 10.1016/j.cyto.2023.156414. Epub 2023 Nov 1.
IL-33 is an alarmin produced by stromal cells and is known to promote airway inflammation. IL-33 is a critical mediator of steroid-unresponsiveness in severe asthma. We have previously shown that IFNγ, a cytokine known to be elevated in airway inflammation and severe asthma, enhances the abundance of IL-33 in bronchial epithelial cells. Previous studies have shown that environmental insults such as particulate matter results in activation of the aryl hydrocarbon receptor (AhR) and IL-33 production. However, the role of AhR in cytokine-mediated IL-33 production is unknown. In this study, we demonstrate that the knockdown of AhR results in significant decrease in IFNγ-mediated IL-33 production and phosphorylation of STAT1 (Y701), in human bronchial epithelial cells. The findings of this report suggest that AhR may be an essential component in IFNγ-mediated IL-33 production in the lungs.
IL-33 是基质细胞产生的警报素，已知可促进气道炎症。IL-33 是严重哮喘中类固醇无反应的关键介质。我们之前已经表明，细胞因子 IFNγ，已知在气道炎症和严重哮喘中升高，可增强支气管上皮细胞中 IL-33 的丰度。先前的研究表明，环境损伤如颗粒物会导致芳香烃受体 (AhR) 的激活和 IL-33 的产生。然而，AhR 在细胞因子介导的 IL-33 产生中的作用尚不清楚。在这项研究中，我们证明 AhR 的敲低导致人支气管上皮细胞中 IFNγ 介导的 IL-33 产生和 STAT1（Y701）磷酸化显著减少。本报告的结果表明，AhR 可能是 IFNγ 介导的肺部 IL-33 产生中的重要组成部分。
