van der Velden V H
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Mediators Inflamm. 1998;7(4):229-37. doi: 10.1080/09629359890910.
GLUCOCORTICOIDS are potent inhibitors of inflammatory processes and are widely used in the treatment of asthma. The anti-inflammatory effects are mediated either by direct binding of the glucocorticoid/glucocorticoid receptor complex to glucocorticoid responsive elements in the promoter region of genes, or by an interaction of this complex with other transcription factors, in particular activating protein-1 or nuclear factor-kappaB. Glucocorticoids inhibit many inflammation-associated molecules such as cytokines, chemokines, arachidonic acid metabolites, and adhesion molecules. In contrast, anti-inflammatory mediators often are up-regulated by glucocorticoids. In vivo studies have shown that treatment of asthmatic patients with inhaled glucocorticoids inhibits the bronchial inflammation and simultaneously improves their lung function. In this review, our current knowledge of the mechanism of action of glucocorticoids and their anti-inflammatory potential in asthma is described. Since bronchial epithelial cells may be important targets for glucocorticoid therapy in asthma, the effects of glucocorticoids on epithelial expressed inflammatory genes will be emphasized.
糖皮质激素是炎症过程的强效抑制剂,广泛用于哮喘治疗。其抗炎作用要么通过糖皮质激素/糖皮质激素受体复合物直接与基因启动子区域的糖皮质激素反应元件结合来介导,要么通过该复合物与其他转录因子(特别是活化蛋白-1或核因子-κB)相互作用来介导。糖皮质激素抑制许多与炎症相关的分子,如细胞因子、趋化因子、花生四烯酸代谢产物和黏附分子。相反,抗炎介质通常会被糖皮质激素上调。体内研究表明,吸入糖皮质激素治疗哮喘患者可抑制支气管炎症,同时改善其肺功能。在这篇综述中,我们阐述了目前关于糖皮质激素作用机制及其在哮喘中的抗炎潜力的知识。由于支气管上皮细胞可能是哮喘糖皮质激素治疗的重要靶点,将重点介绍糖皮质激素对上皮细胞表达的炎症基因的影响。