UMR INSERM U1067 CNRS 7333, Aix-Marseille University, Marseille, France.
Pharmacol Ther. 2013 Dec;140(3):290-305. doi: 10.1016/j.pharmthera.2013.07.008. Epub 2013 Jul 21.
Increasing evidence of a critical role played by the bronchial epithelium in airway homeostasis is opening new therapeutic avenues. Its unique situation at the interface with the environment suggests that the subtle regulation orchestrated by the epithelium between tolerance and specific immune response might be impaired in asthma. Airway mucus is acting as a physical and a biological fluid between the environment and the epithelium, synergistically moved by the cilia. In asthma, excessive mucus production is a hallmark of airway remodeling. Since many years we tried to therapeutically target mucus hypersecretion, but actually this option is still not achieved. The present review discusses the dynamic processes regulating airway mucus production. Airway inflammation is central in current asthma management. Understanding of how the airway epithelium influences the TH2 paradigm in response to deleterious agents is improving. The multiple receptors expressed by the airway epithelium are the transducers of the biological signals induced by various invasive agents to develop the most adapted response. Airway remodeling is observed in severe chronic airway diseases and may result from ongoing disturbance of signal transduction and epithelial renewal. Chronic airway diseases such as asthma will require assessment of these epithelial abnormalities to identify phenotypic characteristics associated with predicting a clinical benefit for epithelial-directed therapies.
越来越多的证据表明，支气管上皮在气道稳态中起着关键作用，这为开辟新的治疗途径提供了依据。其与环境相互作用的独特位置提示，上皮细胞在耐受和特异性免疫反应之间进行的微妙调节可能在哮喘中受损。气道黏液作为环境与上皮细胞之间的物理和生物流体，协同纤毛运动。在哮喘中，过度的黏液产生是气道重塑的标志。多年来，我们一直试图通过治疗来靶向黏液高分泌，但实际上这一目标尚未实现。本综述讨论了调节气道黏液产生的动态过程。气道炎症是当前哮喘管理的核心。对气道上皮如何影响 TH2 范式对有害因子的反应的理解正在不断深入。气道上皮细胞表达的多种受体是各种侵袭性因子诱导的生物信号的转导器，以产生最适应的反应。严重的慢性气道疾病会观察到气道重塑，这可能是由于信号转导和上皮更新的持续紊乱所致。哮喘等慢性气道疾病需要评估这些上皮异常，以确定与预测上皮靶向治疗临床获益相关的表型特征。
