Okunishi Katsuhide, Peters-Golden Marc
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 4810--5642, USA.
Biochim Biophys Acta. 2011 Nov;1810(11):1096-102. doi: 10.1016/j.bbagen.2011.02.005. Epub 2011 Feb 23.
Asthma is a common chronic inflammatory disease of the airways characterized by airway obstruction and hyperresponsiveness. Leukotrienes (LTs) are lipid mediators that contribute to many aspects of asthma pathogenesis. As the LT pathway is relatively steroid-resistant, its blockade by alternative strategies is a desirable component of asthma management. Cysteinyl LT (cysLT) receptor 1 antagonists (LTRAs) have been utilized worldwide for more than 10years, and while their efficacy in asthma is well accepted, their limitations are also evident.
In this review, we summarize the biological effects of LTs in asthma, review recent advances in LT receptors, and consider possible new therapeutic targets in the LT pathway that offer the potential to achieve better control of asthma in the future.
CysLTs play pathogenetic roles in many aspects of asthma, and blockade of cysLT receptor 1 by currently available LTRAs is certainly beneficial in disease management. On the other hand, the limitations of LTRAs are also apparent. Recent studies have revealed new receptors for cysLTs other than classical cysLT receptors 1 and 2, as well as the potential importance of LTB(4) in asthma.
Recent findings provide clues to new approaches for targeting the LT pathway that may overcome the current limitations of LTRAs and achieve superior control of asthma. This article is part of a Special Issue entitled: Biochemistry of Asthma.
哮喘是一种常见的慢性气道炎症性疾病，其特征为气道阻塞和高反应性。白三烯（LTs）是脂质介质，在哮喘发病机制的许多方面都有作用。由于LT途径相对激素抵抗，通过替代策略阻断该途径是哮喘管理中一个理想的组成部分。半胱氨酰白三烯（cysLT）受体1拮抗剂（LTRAs）已在全球使用超过10年，虽然它们在哮喘中的疗效已得到广泛认可，但其局限性也很明显。
在本综述中，我们总结了LTs在哮喘中的生物学效应，回顾了LT受体的最新进展，并考虑了LT途径中可能的新治疗靶点，这些靶点有可能在未来实现对哮喘更好的控制。
CysLTs在哮喘的许多方面发挥致病作用，目前可用的LTRAs阻断cysLT受体1在疾病管理中肯定是有益的。另一方面，LTRAs的局限性也很明显。最近的研究揭示了除经典的cysLT受体1和2之外的cysLTs新受体，以及LTB(4)在哮喘中的潜在重要性。
最近的研究结果为靶向LT途径的新方法提供了线索，这些方法可能克服目前LTRAs的局限性并实现对哮喘的更好控制。本文是名为：哮喘生物化学的特刊的一部分。
