哮喘治疗的生化基础。
Biochemical basis of asthma therapy.
机构信息
National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom.
出版信息
J Biol Chem. 2011 Sep 23;286(38):32899-905. doi: 10.1074/jbc.R110.206466. Epub 2011 Jul 28.
Abstract
Current therapy for asthma is highly effective. β(2)-Adrenergic receptor (β(2)AR) agonists are the most effective bronchodilators and relax airway smooth muscle cells through increased cAMP concentrations and directly opening large conductance Ca(2+) channels. β(2)AR may also activate alternative signaling pathways that may have detrimental effects in asthma. Glucocorticoids are the most effective anti-inflammatory treatments and switch off multiple activated inflammatory genes through recruitment of histone deacetylase-2, activating anti-inflammatory genes, and through increasing mRNA stability of inflammatory genes. There are beneficial molecular interactions between β(2)AR and glucocorticoid-activated pathways. Understanding these signaling pathways may lead to even more effective therapies in the future.
摘要
目前的哮喘治疗方法非常有效。β（2）-肾上腺素能受体（β（2）AR）激动剂是最有效的支气管扩张剂，通过增加 cAMP 浓度和直接打开大电导钙（2+）通道来松弛气道平滑肌细胞。β（2）AR 也可能激活其他信号通路，这些通路在哮喘中可能有不利影响。糖皮质激素是最有效的抗炎治疗方法，通过招募组蛋白去乙酰化酶-2、激活抗炎基因，以及增加炎症基因的 mRNA 稳定性，从而关闭多个激活的炎症基因。β（2）AR 和糖皮质激素激活途径之间存在有益的分子相互作用。了解这些信号通路可能会导致未来更有效的治疗方法。
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