Halayko Andrew J, Amrani Yassine
Departments of Physiology, Internal Medicine, and Pediatrics and Child Health, University of Manitoba, Manitoba, Canada.
Respir Physiol Neurobiol. 2003 Sep 16;137(2-3):209-22. doi: 10.1016/s1569-9048(03)00148-4.
Recent evidence points to progressive structural change in the airway wall, driven by chronic local inflammation, as a fundamental component for development of irreversible airway hyperresponsiveness. Acute and chronic inflammation is orchestrated by cytokines from recruited inflammatory cells, airway myofibroblasts and myocytes. Airway myocytes exhibit functional plasticity in their capacity for contraction, proliferation, and synthesis of matrix protein and cytokines. This confers a principal role in driving different components of the airway remodeling process, and mediating constrictor hyperresponsiveness. Functional plasticity of airway smooth muscle (ASM) is regulated by an array of environmental cues, including cytokines, which mediate their effects through receptors and a number of intracellular signaling pathways. Despite numerous studies of the cellular effects of cytokines on cultured airway myocytes, few have identified how intracellular signaling pathways modulate or induce these cellular responses. This review summarizes current understanding of these concepts and presents a model for the effects of inflammatory mediators on functional plasticity of ASM in asthma.
近期证据表明，由慢性局部炎症驱动的气道壁渐进性结构变化是不可逆气道高反应性发展的基本组成部分。急性和慢性炎症由募集的炎症细胞、气道肌成纤维细胞和肌细胞产生的细胞因子协调。气道肌细胞在收缩、增殖以及基质蛋白和细胞因子合成能力方面表现出功能可塑性。这赋予其在驱动气道重塑过程的不同组成部分以及介导收缩性高反应性方面的主要作用。气道平滑肌（ASM）的功能可塑性受一系列环境信号调节，包括细胞因子，这些细胞因子通过受体和许多细胞内信号通路介导其作用。尽管对细胞因子对培养气道肌细胞的细胞效应进行了大量研究，但很少有研究确定细胞内信号通路如何调节或诱导这些细胞反应。本综述总结了对这些概念的当前理解，并提出了炎症介质对哮喘中ASM功能可塑性影响的模型。
