IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic effect of IL-36γ
IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic effect of IL-36γ
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DOI：
10.1093/cei/uxad099
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发表时间：
2023-09-23
影响因子：
4.6
通讯作者：
Zhang，Tian-Tuo
中科院分区：
文献类型：
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作者：
Zhang，Min;Zhou，Jian-Xia;Zhang，Tian-Tuo
气道重塑是哮喘的主要特征。白细胞介素（IL）-36γ在哮喘中显著上调并促进气道高反应性（AHR），但其在气道重塑中的作用尚不清楚。本研究旨在探讨IL-36γ在气道重塑中的作用，以及IL-38是否能通过阻断IL-36γ的作用减轻慢性哮喘气道重塑。在吸入屋尘螨（HDM）的小鼠中定量IL-36γ。在对小鼠施用IL-36γ后评估肺组织中的细胞外基质（ECM）沉积和AHR。哮喘小鼠经IL-38或阻断IL-36受体（IL-36 R）治疗后，评价气道炎症、AHR和重塑。在体外定量IL-36γ和IL-38刺激肺成纤维细胞的作用。在HDM诱导的哮喘小鼠肺组织中检测到IL-36γ的表达增加。气管内滴注IL-36γ可显著增加气道周围ECM沉积、AHR和活化的肺成纤维细胞数量。与HDM组相比，IL-38或阻断IL-36 R治疗的哮喘小鼠的气道炎症、AHR、气道重塑和气道周围活化的成纤维细胞数量均明显减轻，IL-36γ在体外促进人肺成纤维细胞（HFL-1）的活化和迁移。IL-38的应用可以对抗IL-36γ诱导的HFL-1细胞的上述生物学过程。提示IL-38可通过阻断IL-36γ的促纤维化作用减轻慢性哮喘气道重塑。IL-36γ可能是一个新的治疗靶点，IL-38是一个潜在的抑制哮喘气道重塑的候选药物。
Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice. Airway inflammation, AHR, and remodeling were evaluated after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The effects of lung fibroblasts stimulated with IL-36γ and IL-38 were quantifiedin vitro. Increased expression of IL-36γ was detected in lung tissues of HDM-induced asthmatic mice. The intratracheal instillation of IL-36γ to mice significantly enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a significant alleviation in the airway inflammation, AHR, airway remodeling, and number of activated fibroblasts around airways as compared with the HDM group.In vitro, IL-36γ promoted the activation and migration of human lung fibroblasts (HFL-1). The administration of IL-38 can counteract these biological processes induced by IL-36γ in HFL-1cells. The results indicated that IL-38 can mitigate airway remodeling by blocking the profibrotic effects of IL-36γ in chronic asthma. IL-36γ may be a new therapeutic target, and IL-38 is a potential candidate agent for inhibiting airway remodeling in asthma.