Effects of inhaled β agonist and corticosteroid treatment on nuclear transcription factors in bronchial mucosa in asthma
Effects of inhaled β agonist and corticosteroid treatment on nuclear transcription factors in bronchial mucosa in asthma
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DOI：
10.1136/thx.54.6.488
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发表时间：
1999-06-01
期刊：
影响因子：
10
通讯作者：
Taylor, DR
中科院分区：
文献类型：
--
作者：
Hancox, RJ;Stevens, DA;Taylor, DR
背景-吸入性皮质类固醇和β受体激动剂是哮喘最常用的治疗方法，并且经常联合使用。最近的证据表明，皮质类固醇的许多抗炎作用是由活化的糖皮质激素受体（GR）和其他转录因子如促炎核因子κ B（NF κ B）之间的串扰介导的。β激动剂可以激活转录因子cAMP反应元件结合蛋白（CREB）。GR和CREB之间的相互抑制在体外发生，这提高了皮质类固醇和β激动剂药物之间的负相互作用的可能性。进行一项研究，以确定这些相互作用是否发生在治疗过程中与β（2），激动剂和皮质类固醇在asthen. Methods的7名受试者参加了一项随机，安慰剂对照，交叉研究的6周治疗吸入布地奈德（400微克，每天两次），特布他林（1毫克，每天四次），并联合治疗招募。每次治疗后取支气管粘膜活检标本，分析GR、CREB和NF κ B的DNA结合活性。
Background-Inhaled corticosteroids and beta agonists are the most commonly used treatments in asthma and are often used together. Recent evidence suggests that many of the anti-inflammatory actions of corticosteroids are mediated by cross-talk between the activated glucocorticoid receptor (GR) and other transcription factors such as the pro-inflammatory nuclear factor kappa B (NF kappa B). Beta agonists can activate the transcription factor cAMP response element binding protein (CREB). A mutual inhibition between GR and CREB occurs in vitro which raises the possibility of a negative interaction between corticosteroid and beta agonist drugs. A study was undertaken to determine whether these interactions occur during treatment with beta(2), agonists and corticosteroids in asthma.Methods-Seven subjects who were participating in a randomised, placebo controlled, crossover study of six weeks treatment with inhaled budesonide (400 mu g twice daily), terbutaline (1 mg four times daily), and combined treatment were recruited. Biopsy samples of the bronchial mucosa were obtained after each treatment and analysed for the DNA binding activity of GR, CREB, and NF kappa B.Results-Budesonide increased GR activity (p