内皮素-1介导烟曲霉诱导的气道炎症和重塑
2019/06/28
摘要
背景：哮喘是一种气道的慢性炎症状态，对空气传播的真菌如烟曲霉敏感的患者有更严重的哮喘。支气管上皮下层的增厚是哮喘严重程度的促成因素，目前尚无治疗方法。气道上皮作为吸入孢子的初始防御屏障，协调炎症反应并促成上皮下纤维化。
目的：我们的目的是分析气道上皮响应烟曲霉的促纤维化因子的产生，以提出新的抗纤维化策略用于真菌诱导的哮喘。
方法：我们评估了人气道上皮细胞和暴露于烟曲霉孢子或分泌的真菌因子的小鼠对关键促纤维化因子TGF-β1，TGF-β2，骨膜素和内皮素-1的诱导。
结果：烟曲霉特异性地在体外引起上皮细胞产生内皮素-1，但没有任何其他促纤维化因子。烟曲霉还在小鼠肺中诱导内皮素-1的产生，者与广泛的炎症和气道重塑有关。使用选择性内皮素-1受体拮抗剂，我们首次证明内皮素-1驱动烟曲霉引起的气道重塑和炎症的许多特征。
结论：我们的研究结果与内皮素-1水平升高有助于上皮下增厚的假设一致，并强调该因素可作为难治疗的真菌诱发哮喘的治疗靶点。
Endothelin‐1 mediates Aspergillus fumigatus‐induced airway inflammation and remodelling
Briony Labram, Sara Namvar, Tracy Hussell, Sarah E. Herrick
Clin Exp Allergy. 2019 Jun;49(6):861-873.
Abstract
BACKGROUND: Asthma is a chronic inflammatory condition of the airways and patients sensitized to airborne fungi such as Aspergillus fumigatus have more severe asthma. Thickening of the bronchial subepithelial layer is a contributing factor to asthma severity for which no current treatment exists. Airway epithelium acts as an initial defence barrier to inhaled spores, orchestrating an inflammatory response and contributing to subepithelial fibrosis.
OBJECTIVE: We aimed to analyse the production of pro-fibrogenic factors by airway epithelium in response to A fumigatus, in order to propose novel anti-fibrotic strategies for fungal-induced asthma.
METHODS: We assessed the induction of key pro-fibrogenic factors, TGF-β1, TGF-β2, periostin and endothelin-1, by human airway epithelial cells and in mice exposed to A fumigatus spores or secreted fungal factors.
RESULTS: Aspergillus fumigatus specifically caused production of endothelin-1 by epithelial cells in vitro but not any of the other pro-fibrogenic factors assessed. A fumigatus also induced endothelin-1 in murine lungs, associated with extensive inflammation and airway remodelling. Using a selective endothelin-1 receptor antagonist, we demonstrated for the first time that endothelin-1 drives many features of airway remodelling and inflammation elicited by A fumigatus.
CONCLUSION: Our findings are consistent with the hypothesis that elevated endothelin-1 levels contribute to subepithelial thickening and highlight this factor as a possible therapeutic target for difficult-to-treat fungal-induced asthma.
背景：哮喘是一种气道的慢性炎症状态，对空气传播的真菌如烟曲霉敏感的患者有更严重的哮喘。支气管上皮下层的增厚是哮喘严重程度的促成因素，目前尚无治疗方法。气道上皮作为吸入孢子的初始防御屏障，协调炎症反应并促成上皮下纤维化。
目的：我们的目的是分析气道上皮响应烟曲霉的促纤维化因子的产生，以提出新的抗纤维化策略用于真菌诱导的哮喘。
方法：我们评估了人气道上皮细胞和暴露于烟曲霉孢子或分泌的真菌因子的小鼠对关键促纤维化因子TGF-β1，TGF-β2，骨膜素和内皮素-1的诱导。
结果：烟曲霉特异性地在体外引起上皮细胞产生内皮素-1，但没有任何其他促纤维化因子。烟曲霉还在小鼠肺中诱导内皮素-1的产生，者与广泛的炎症和气道重塑有关。使用选择性内皮素-1受体拮抗剂，我们首次证明内皮素-1驱动烟曲霉引起的气道重塑和炎症的许多特征。
结论：我们的研究结果与内皮素-1水平升高有助于上皮下增厚的假设一致，并强调该因素可作为难治疗的真菌诱发哮喘的治疗靶点。
(黄丹1 张红萍1 王刚2，3 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Clin Exp Allergy. 2019 Jun;49(6):861-873.）
（Clin Exp Allergy. 2019 Jun;49(6):861-873.）
Endothelin‐1 mediates Aspergillus fumigatus‐induced airway inflammation and remodelling
Briony Labram, Sara Namvar, Tracy Hussell, Sarah E. Herrick
Clin Exp Allergy. 2019 Jun;49(6):861-873.
Abstract
BACKGROUND: Asthma is a chronic inflammatory condition of the airways and patients sensitized to airborne fungi such as Aspergillus fumigatus have more severe asthma. Thickening of the bronchial subepithelial layer is a contributing factor to asthma severity for which no current treatment exists. Airway epithelium acts as an initial defence barrier to inhaled spores, orchestrating an inflammatory response and contributing to subepithelial fibrosis.
OBJECTIVE: We aimed to analyse the production of pro-fibrogenic factors by airway epithelium in response to A fumigatus, in order to propose novel anti-fibrotic strategies for fungal-induced asthma.
METHODS: We assessed the induction of key pro-fibrogenic factors, TGF-β1, TGF-β2, periostin and endothelin-1, by human airway epithelial cells and in mice exposed to A fumigatus spores or secreted fungal factors.
RESULTS: Aspergillus fumigatus specifically caused production of endothelin-1 by epithelial cells in vitro but not any of the other pro-fibrogenic factors assessed. A fumigatus also induced endothelin-1 in murine lungs, associated with extensive inflammation and airway remodelling. Using a selective endothelin-1 receptor antagonist, we demonstrated for the first time that endothelin-1 drives many features of airway remodelling and inflammation elicited by A fumigatus.
CONCLUSION: Our findings are consistent with the hypothesis that elevated endothelin-1 levels contribute to subepithelial thickening and highlight this factor as a possible therapeutic target for difficult-to-treat fungal-induced asthma.
上一篇：
成人哮喘发作的风险随着过敏性多发性疾病的数量增加而增加，随着年龄的增长而降低
下一篇：
在严重哮喘治疗的试验中，对维持药物的依从性评估不足会导致效能损失和成本增加，系统的文献回顾和模型研究的结果
