Potential therapeutic targets for steroid-resistant asthma.
Potential therapeutic targets for steroid-resistant asthma.
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DOI：
10.2174/138945010791591412
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发表时间：
2010-07
影响因子：
3.2
通讯作者：
Wan Wang;Jing Li;P. Foster;P. Hansbro;Ming Yang
中科院分区：
文献类型：
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作者：
Wan Wang;Jing Li;P. Foster;P. Hansbro;Ming Yang
糖皮质激素是哮喘治疗的中流砥柱，可有效治疗哮喘急性加重。然而，一小部分哮喘患者，通常患有严重哮喘，即使对全身给予大剂量糖皮质激素也反应不佳，这种情况被称为“类固醇抵抗性哮喘”。这个队列虽然很小，但约占哮喘总医疗保健费用的50%。对糖皮质激素作用机制的新研究拓宽和加深了我们对糖皮质激素耐药性的认识。在这里，我们回顾了类固醇抵抗性哮喘的重要性和特点，介导糖皮质激素功能的机制，导致这种疾病的发展和潜在的治疗方法来逆转对治疗的抵抗。细胞和分子因子，受体和复杂的信号通路都有牵连。事实上，根据分子生物学研究，细胞内转录因子的过度激活、组蛋白去乙酰化酶的受损、表观遗传（如miR-18和miR-124a）以及其他因素(如维生素D、p -糖蛋白170、巨噬细胞迁移抑制因子和T辅助17细胞以及先天免疫相关因素（如ifn - γ和LPS）可能导致糖皮质激素耐药。彻底了解类固醇抵抗性哮喘的发病机制将有助于开发更有效的药物来治疗该病。
Glucocorticoids are the mainstay of asthma management and effectively treat acute exacerbations of asthma. However, a small subset of asthmatics, usually with severe asthma, respond poorly even to systemic administration of high-dose glucocorticoids and this condition is termed "steroid-resistant asthma". This cohort, although small, accounts for approximately 50% of total health care cost for asthma. New investigations into the mechanisms of glucocorticoid action have broadened and deepened our understanding of glucocorticoid resistance. Here we review the importance and characteristics of steroid resistant asthma, the mechanisms that mediate the function of glucocorticoids and that lead to the development of this disease and potential therapies to reverse resistance to treatment. Cellular and molecular factors, receptors and complex signalling pathways have all been implicated. Indeed, based on molecular biological studies, excessive activation of intracellular transcription factors, impaired histone deacetylase, and epigenetic (such as miR-18 and miR-124a) as well as other factors (e.g. vitamin D, P-glycoprotein 170, and macrophage migration inhibitory factor and T helper 17 cells and factors related to innate immunity (such as IFN-gamma and LPS)) may result in glucocorticoid resistance. A thorough understanding of the pathogenesis of steroid resistant asthma will help to develop more efficacious agents for the treatment of the disease.