Zhang X, Moilanen E, Kankaanranta H
Medical School, FIN-33014, University of Tampere, Tampere, Finland.
Eur J Pharmacol. 2000 Oct 20;406(3):325-32. doi: 10.1016/s0014-2999(00)00690-7.
Beclomethasone, budesonide, dexamethasone, and fluticasone propionate enhanced human eosinophil apoptosis in a concentration-dependent manner in vitro as assessed by flow cytometric analysis and morphological analysis. The order of potency was fluticasone propionate (EC(50) 3.7+/-1.8 nM) approximately budesonide (EC(50) 5.0+/-1.7 nM)>beclomethasone (EC(50) 51+/-19 nM)>dexamethasone (EC(50) 303+/-40 nM). Hydrocortisone, prednisolone, and prednisone (up to 1 microM) did not induce any significant increase in eosinophil apoptosis. The apoptosis promoting effects of glucocorticoids on eosinophils were reversed by an antagonist of glucocorticoid receptor mifepristone. The survival-prolonging effect of tumor necrosis factor (TNF)-alpha was reversed by dexamethasone and fluticasone (1 microM). In contrast, fluticasone, and dexamethasone (1 microM) did not reverse the survival-prolonging effects of interleukins-3 and -5 or granulocyte-macrophage colony-stimulating factor (GM-CSF). The results suggest that fluticasone and budesonide induce eosinophil apoptosis at clinically achievable drug concentrations via an effect on glucocorticoid receptor.
通过流式细胞术分析和形态学分析评估，倍氯米松、布地奈德、地塞米松和丙酸氟替卡松在体外以浓度依赖性方式增强人嗜酸性粒细胞凋亡。效力顺序为丙酸氟替卡松（EC50 3.7±1.8 nM）约等于布地奈德（EC50 5.0±1.7 nM）＞倍氯米松（EC50 51±19 nM）＞地塞米松（EC50 303±40 nM）。氢化可的松、泼尼松龙和泼尼松（高达1 microM）未诱导嗜酸性粒细胞凋亡有任何显著增加。糖皮质激素受体拮抗剂米非司酮可逆转糖皮质激素对嗜酸性粒细胞的凋亡促进作用。地塞米松和丙酸氟替卡松（1 microM）可逆转肿瘤坏死因子（TNF）-α的存活延长作用。相比之下，丙酸氟替卡松和地塞米松（1 microM）不能逆转白细胞介素-3和-5或粒细胞-巨噬细胞集落刺激因子（GM-CSF）的存活延长作用。结果表明，丙酸氟替卡松和布地奈德在临床可达到的药物浓度下通过对糖皮质激素受体的作用诱导嗜酸性粒细胞凋亡。
