Department of Clinical Chemistry and Molecular Diagnostics, Biomedical Research Center (BMFZ), Hospital of the Philipps-University, 35043 Marburg, Germany.
J Occup Med Toxicol. 2008 Feb 27;3 Suppl 1(Suppl 1):S4. doi: 10.1186/1745-6673-3-S1-S4.
Over the last decade mouse models of experimental asthma proved to be a valuable tool for the investigation of mechanisms that underlie acute allergic airway inflammation and development of airway hyperresponsiveness, two of the hallmarks of human asthma. Nevertheless, these acute models fail to reflect the aspects of this chronic disease because they do not represent any signs of chronicity and airway remodelling as it is defined by subepithelial fibrosis, goblet cell hyperplasia and airway smooth muscle cell hypertrophy. Recent mouse models were successful in overcoming these limitations by using chronic allergen-challenges. These new models of chronic experimental asthma now proved as a novel tool to examine the complex interaction of infiltrating inflammatory cells and structural cells such as fibroblasts and smooth muscle cells that ultimately leads to airway remodelling and stable airflow limitation. Recent studies clearly demonstrated that T helper 2 (TH2) cells and their typical cytokines play a critical role not only in airway inflammation but also in the development of airway remodelling. Since the transcription factor GATA-3 is essential for TH2 cell development and the production of several TH2 type cytokines this intracellular molecule represents a new promising target for therapeutic intervention in asthma that might even effect airway remodelling.
在过去的十年中，实验性哮喘的小鼠模型已被证明是研究急性过敏性气道炎症和气道高反应性发展的机制的有价值的工具，这两个机制是人类哮喘的两个主要特征。然而，这些急性模型未能反映出这种慢性疾病的各个方面，因为它们没有表现出任何慢性和气道重塑的迹象，如黏膜下纤维化、杯状细胞增生和气道平滑肌细胞肥大等。最近的小鼠模型通过使用慢性变应原挑战成功地克服了这些局限性。这些慢性实验性哮喘的新模型现在已被证明是一种研究浸润性炎症细胞和结构细胞（如成纤维细胞和平滑肌细胞）之间复杂相互作用的新工具，这些细胞最终导致气道重塑和稳定的气流受限。最近的研究清楚地表明，辅助性 T 细胞 2（TH2）细胞及其典型细胞因子不仅在气道炎症中发挥关键作用，而且在气道重塑的发展中也发挥关键作用。由于转录因子 GATA-3 对于 TH2 细胞的发育和几种 TH2 型细胞因子的产生至关重要，因此这个细胞内分子代表了哮喘治疗干预的一个新的有前途的靶点，甚至可能影响气道重塑。
