The Brooke Laboratories, Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom.
Proc Am Thorac Soc. 2009 Dec;6(8):678-82. doi: 10.1513/pats.200907-067DP.
The bronchial epithelium is the barrier to the external environment and plays a vital role in protection of the internal milieu of the lung. It functions within the epithelial-mesenchymal trophic unit to control the local microenvironment and help maintain tissue homeostasis. However, in asthma, chronic perturbation of these homeostatic mechanisms leads to alterations in the structure of the airways, termed remodeling. Damage to the epithelium is now recognized to play a key role in driving airway remodeling. We have postulated that epithelial susceptibility to environmental stress and injury together with impaired repair responses results in generation of signals that act on the underlying mesenchyme to propagate and amplify inflammatory and remodeling responses in the submucosa. Many types of challenges to the epithelium, including pathogens, allergens, environmental pollutants, cigarette smoke, and even mechanical forces, can elicit production of mediators by the epithelium, which can be translated into remodeling responses by the mesenchyme. Several important mediators of remodeling have been identified, most notably transforming growth factor-beta, which is released from damaged/repairing epithelium or in response to inflammatory mediators, such as IL-13. The cross talk between the epithelium and the underlying mesenchyme to drive remodeling responses is considered in the context of subepithelial fibrosis and potential pathogenetic mechanisms linked to the asthma susceptibility gene, a disintegrin and metalloprotease (ADAM)33.
支气管上皮是对外界环境的屏障，在保护肺部内部环境方面起着至关重要的作用。它在上皮-间充质营养单位内发挥作用，以控制局部微环境并帮助维持组织内稳态。然而，在哮喘中，这些内稳态机制的慢性紊乱导致气道结构发生改变，称为重塑。目前认为上皮细胞对环境应激和损伤的敏感性以及受损的修复反应导致产生信号，这些信号作用于下面的间充质，在黏膜下层传播和放大炎症和重塑反应。许多类型的上皮细胞挑战，包括病原体、过敏原、环境污染物、香烟烟雾，甚至机械力，都可以引发上皮细胞产生介质，这些介质可以被间充质转化为重塑反应。已经确定了几种重要的重塑介质，其中最显著的是转化生长因子-β，它可以从受损/修复的上皮细胞释放，也可以响应于炎症介质，如 IL-13。在讨论潜在的致病机制时，需要考虑上皮细胞和下面的间充质之间的信号转导，以驱动重塑反应，这些机制与哮喘易感基因 a 型血小板结合蛋白（ADAM）33 有关。
