Epithelial-mesenchymal communication in the pathogenesis of chronic asthma.
Epithelial-mesenchymal communication in the pathogenesis of chronic asthma.
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DOI：
10.1513/pats.2306034
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Davies, Donna E
中科院分区：
文献类型：
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作者：
Holgate, Stephen T;Holloway, John;Davies, Donna E
尽管 Th-2 介导的炎症是哮喘的关键治疗靶点，但其与气道结构和功能改变的关系在很大程度上尚不清楚。除了炎症之外，哮喘是一种涉及气道上皮的疾病，它更容易受到环境损伤，并通过受损的愈合来应对这种情况。这建立了一种能够维持慢性炎症和重塑的慢性伤口情况。这种反应是上皮间质单位激活的结果，涉及属于成纤维细胞生长因子、表皮生长因子和转化生长因子-β家族的生长因子的相互活性。儿童哮喘发作时或哮喘发作前发生的气道结构变化与炎症无关的观察结果可能表明，在 Th-2 炎症反应持续之前需要进行预建模。一旦建立，包括成纤维细胞、平滑肌、神经和上皮细胞在内的组成性气道细胞的功能改变，就会提供异常的微环境，在其中产生一组单独的信号，这些信号支撑由病毒、污染物和过敏原引发的哮喘恶化的急性/亚急性炎症特征。
Although Th-2-mediated inflammation is a key therapeutic target in asthma, its relationship to altered structure and functions of the airways is largely unknown. In addition to inflammation, asthma is a disorder involving the airway epithelium that is more vulnerable to environmental injury and responds to this by impaired healing. This establishes a chronic wound scenario that is capable of sustaining chronic inflammation as well as remodeling. This response occurs as a consequence of activation of the epithelial-mesenchymal unit, involving reciprocal activities of growth factors belonging to the fibroblast growth factor, epidermal growth factor, and transforming growth factor-beta families. The observation that structural changes in the airways in children at or before the onset of asthma occurs irrespective of inflammation might suggest that premodeling is required before Th-2 inflammatory responses can be sustained. Once established, altered function of constitutive airway cells, including fibroblasts, smooth muscle, nerves, and the epithelium, provides an abnormal microenvironment in which to generate a separate set of signals that underpin the acute/subacute inflammation characteristic of asthma exacerbations, triggered by viruses, pollutants, and allergens.