Differential control of eosinophil survival by glucocorticoids
Differential control of eosinophil survival by glucocorticoids
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DOI：
10.1023/b:appt.0000012126.06126.c4
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发表时间：
2004-01-01
期刊：
影响因子：
7.2
通讯作者：
Miesfeld, RL
中科院分区：
文献类型：
--
作者：
Bloom, JW;Chacko, J;Miesfeld, RL
糖皮质激素是治疗嗜酸性粒细胞相关疾病（例如哮喘和过敏）的有效药物。先前的研究表明，糖皮质激素会增加嗜酸性粒细胞凋亡并阻断次最大浓度的白细胞介素-5 (IL-5) 的生存效应。我们研究了在较高浓度 IL-5（1 ng/ml）存在下糖皮质激素对嗜酸性粒细胞存活的影响，该浓度与哮喘患者支气管肺泡灌洗液和痰标本中的 IL-5 水平相当。与在次最大浓度IL-5存在下的孵育相反，在培养72小时后，向含有1ng/ml IL-5的培养基中添加地塞米松(DEX)导致嗜酸性粒细胞活力从58+/-6.9%显着增加至87+/-2.4%(p<0.005)。我们发现 RU486 阻断了 DEX 对细胞活力的影响，证实了糖皮质激素受体功能是必需的。我们研究了糖皮质激素对嗜酸性粒细胞存活的增强可能是由于对 IL-5 受体表达的影响的可能性。我们的结果表明，与单独的IL-5相比，用含有IL-5加DEX的培养基培养24小时后，与IL-5相关的IL-5受体α-亚基表达的降低被显着阻断。人们很容易推测，在IL-5浓度升高的情况下观察到的糖皮质激素对嗜酸性粒细胞存活的增强可能是导致哮喘中糖皮质激素抵抗的机制。
Glucocorticoids are effective drugs for eosinophil- related disorders, such as asthma and allergy. Previous studies have demonstrated that glucocorticoids increase eosinophil apoptosis and block the survival effect of submaximal concentrations of interleukin- 5 ( IL- 5). We investigated the effect of glucocorticoids on eosinophil survival in the presence of a higher concentration of IL- 5 ( 1 ng/ ml), comparable to IL- 5 levels in bronchoalveolar lavage and sputum specimens from patients with asthma. In contrast to incubation in the presence of submaximal concentrations of IL- 5, the addition of dexamethasone ( DEX) to media containing 1 ng/ ml IL- 5 led to a significant increase in eosinophil cell viability from 58 +/- 6.9% to 87 +/- 2.4% ( p< 0.005) after 72 hours in culture. We found that RU486 blocked the DEX effect on cell viability confirming that glucocorticoid receptor functions are required. We investigated the possibility that the glucocorticoid enhancement of eosinophil survival may be due to an effect on IL- 5 receptor expression. Our results show that the IL- 5 associated decrease in IL- 5 receptor α- subunit expression was blocked significantly after 24 hrs in culture with media containing IL- 5 plus DEX compared to IL- 5 alone. It is tempting to speculate that the observed glucocorticoid enhancement of eosinophil survival in the presence of elevated concentrations of IL- 5 could be a mechanism that contributes to glucocorticoid resistance in asthma.