Abstract:
Asthma is deemed an inflammatory disease, yet the defining diagnostic feature is mechanical bronchoconstriction. We previously discovered a conserved process called cell extrusion that drives homeostatic epithelial cell death when cells become too crowded. In this work, we show that the pathological crowding of a bronchoconstrictive attack causes so much epithelial cell extrusion that it damages the airways, resulting in inflammation and mucus secretion in both mice and humans. Although relaxing the airways with the rescue treatment albuterol did not affect these responses, inhibiting live cell extrusion signaling during bronchoconstriction prevented all these features. Our findings show that bronchoconstriction causes epithelial damage and inflammation by excess crowding-induced cell extrusion and suggest that blocking epithelial extrusion, instead of the ensuing downstream inflammation, could prevent the feed-forward asthma inflammatory cycle.
摘要:
哮喘被认为是一种炎症性疾病,然而,明确的诊断特征是机械支气管收缩。我们以前发现了一种保守的过程,称为细胞挤压,当细胞变得过于拥挤时,它会驱动稳态上皮细胞死亡。在这项工作中,我们表明,支气管收缩性攻击的病理性拥挤会导致如此多的上皮细胞挤压,从而损害气道,导致小鼠和人类的炎症和粘液分泌。尽管使用沙丁胺醇抢救治疗来放松气道并不影响这些反应,在支气管收缩过程中抑制活细胞挤出信号阻止了所有这些特征。我们的研究结果表明,支气管收缩通过过度拥挤诱导的细胞挤压引起上皮损伤和炎症,并表明阻断上皮挤压,而不是随之而来的下游炎症,可以预防前馈哮喘炎症循环。