School of Pharmacy, The University of Technology Sydney, NSW, Australia.
Br J Pharmacol. 2012 Nov;167(6):1161-76. doi: 10.1111/j.1476-5381.2012.01984.x.
Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern-recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen- and host-derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome-wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand-RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions.
哮喘和慢性阻塞性肺疾病（COPD）是呼吸道异质性炎症性疾病，其特征为气流阻塞。现在已经很清楚，导致哮喘和 COPD 气道病变的环境因素，包括过敏原、病毒、臭氧和香烟烟雾，通过直接或间接引起内源性配体的释放，激活了称为模式识别受体的先天免疫受体。因此，现在有大量的研究活动集中在理解模式识别受体如何维持气道炎症反应，以及这些机制如何在治疗上得到靶向。在慢性气道疾病中，最近引起关注的一种模式识别受体是晚期糖基化终产物受体（RAGE）。RAGE 是细胞表面免疫球蛋白超家族的成员，它识别病原体和宿主来源的内源性配体，从而启动对组织损伤、感染和炎症的免疫反应。尽管 RAGE 在肺生理学和病理生理学中的作用尚不清楚，但最近的全基因组关联研究已经将 RAGE 基因多态性与气流阻塞联系起来。此外，来自动物和临床研究的累积数据显示，在慢性气道疾病中，RAGE 及其配体的表达增加，同时 RAGE 信号转导的内源性抑制剂可溶性 RAGE 的表达减少。在这篇综述中，我们讨论了配体-RAGE 轴在哮喘和 COPD 中的最新研究，强调了未来研究的重要领域，并讨论了如何在这些疾病中利用该轴获得治疗益处。
