Mechanisms of corticosteroid resistance in asthmatic patients.
Mechanisms of corticosteroid resistance in asthmatic patients.
复制标题
哮喘患者皮质类固醇抵抗的机制。
DOI：
10.1159/000237544
复制
发表时间：
1997
影响因子：
2.8
通讯作者：
Tak H. Lee
中科院分区：
文献类型：
--
作者：
Stephen J. Lane;Tak H. Lee
皮质类固醇抵抗（CR）哮喘与疾病慢性化、更常见的哮喘家族史以及外周血单核细胞对糖皮质激素抑制作用的体外和体内反应性受损有关。CR哮喘与地塞米松对下丘脑-垂体-肾上腺轴和骨转换生化指标的正常抑制有关，表明糖皮质激素抵抗现象是炎症性白细胞特有的，这些患者同样有发生“库欣样”副作用的风险。在CR哮喘患者中，我们无法检测到糖皮质激素给药的生物利用度改变、配体结合受损或活化糖皮质激素受体（GR）复合物核转位或GR cDNA结构异常。我们最近证实，与皮质类固醇敏感性哮喘相比，CR哮喘与外周血单个核细胞中GR降低和AP-1（Fos; Jun）DNA结合增加有关。这些结果强调了在CR哮喘中，AP-1/GR相互作用在糖皮质激素作用中的中心作用。
Corticosteroid-resistant (CR) asthma is associated with disease chronicity, a more frequent family history of asthma and impaired in vitro and in vivo responsiveness of peripheral blood mononuclear cells to the suppressive effects of glucocorticoids. CR asthma is associated with normal suppression of the hypothalamic-pituitary-adrenal axis and of biochemical indices of bone turnover by dexamethasone, indicating that the phenomenon of glucocorticoid resistance is specific to inflammatory leukocytes and that these patients are equally at risk of developing 'cushingoid' side effects. We have been unable to detect altered bioavailability of administered glucocorticoid, impaired ligand binding or nuclear translocation of the activated glucocorticoid receptor (GR) complex or structural abnormalities of the GR cDNA in our population of CR asthmatics. We have recently demonstrated that CR asthma is associated with decreased GR and increased AP-1 (Fos; Jun) DNA binding in peripheral blood mononuclear cells as compared to corticosteroid-sensitive asthma. These results highlight the central role of the AP-1/GR interactions in glucocorticoid action in CR asthma.