Caramori Gaetano, Adcock Ian
Department of Thoracic Medicine, National Heart and Lung Institute at Imperial College School of Science, Technology and Medicine, Dovehouse Street, London, SW3 6LY, UK.
Curr Drug Targets Inflamm Allergy. 2005 Aug;4(4):455-63. doi: 10.2174/1568010054526331.
Asthmatic inflammation involves the recruitment and activation of inflammatory cells, and changes in the structural cells of the lung and asthma are characterized by an increased expression of components of the inflammatory cascade including cytokines, chemokines, growth factors, enzymes, receptors and adhesion molecules. The increased expression of these proteins seen in asthma is generally the result of enhanced gene transcription, since many of the genes are not expressed in normal cells but are induced in a cell-specific manner during the inflammatory process. There is clear evidence that neutrophils, long thought of as being transcriptionally inert, can respond to stimuli to induce inflammatory genes. Glucocorticoids are very effective in controlling the inflammation seen in asthmatic airways. Beyond their recognized actions on eosinophil and neutrophil apoptosis, glucocorticoids have profound effects on the chemotaxis, activation and release of mediators from granulocytes (eosinophils, neutrophils and basophils). Few mechanistic studies are available in these cells, but it appears that in granulocytes, glucocorticoids target the same signaling pathways, such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), that are important in other cells. We summarize these known mechanisms at the end of this review.
哮喘炎症涉及炎症细胞的募集和激活，肺部结构细胞的变化以及哮喘的特征是炎症级联反应的成分表达增加，包括细胞因子、趋化因子、生长因子、酶、受体和黏附分子。在哮喘中所见的这些蛋白质表达增加通常是基因转录增强的结果，因为许多基因在正常细胞中不表达，但在炎症过程中以细胞特异性方式被诱导表达。有明确证据表明，长期以来被认为转录惰性的中性粒细胞能够对刺激作出反应以诱导炎症基因。糖皮质激素在控制哮喘气道炎症方面非常有效。除了其对嗜酸性粒细胞和中性粒细胞凋亡的公认作用外，糖皮质激素对粒细胞（嗜酸性粒细胞、中性粒细胞和嗜碱性粒细胞）的趋化性、激活和介质释放有深远影响。关于这些细胞的机制研究很少，但在粒细胞中，糖皮质激素似乎靶向与其他细胞中重要的相同信号通路，如核因子κB（NF-κB）和激活蛋白-1（AP-1）。我们在本综述末尾总结了这些已知机制。
