Banno Asoka, Reddy Aravind T, Lakshmi Sowmya P, Reddy Raju C
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213.
Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA 15240.
Nucl Receptor Res. 2018;5. doi: 10.11131/2018/101306. Epub 2017 Dec 11.
Asthma affects approximately 300 million people worldwide, significantly impacting quality of life and healthcare costs. While current therapies are effective in controlling many patients' symptoms, a large number continue to experience exacerbations or treatment-related adverse effects. Alternative therapies are thus urgently needed. Accumulating evidence has shown that the peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors, comprising PPARα, PPARβ/δ, and PPARγ, is involved in asthma pathogenesis and that ligand-induced activation of these receptors suppresses asthma pathology. PPAR agonists exert their anti-inflammatory effects primarily by suppressing pro-inflammatory mediators and antagonizing the pro-inflammatory functions of various cell types relevant to asthma pathophysiology. Experimental findings strongly support the potential clinical benefits of PPAR agonists in the treatment of asthma. We review current literature, highlighting PPARs' key role in asthma pathogenesis and their agonists' therapeutic potential. With additional research and rigorous clinical studies, PPARs may become attractive therapeutic targets in this disease.
哮喘影响着全球约3亿人,对生活质量和医疗成本产生重大影响。虽然目前的治疗方法能有效控制许多患者的症状,但仍有大量患者继续经历病情加重或与治疗相关的不良反应。因此,迫切需要替代疗法。越来越多的证据表明,核激素受体的过氧化物酶体增殖物激活受体(PPAR)家族,包括PPARα、PPARβ/δ和PPARγ,参与哮喘发病机制,并且这些受体的配体诱导激活可抑制哮喘病理。PPAR激动剂主要通过抑制促炎介质和拮抗与哮喘病理生理学相关的各种细胞类型的促炎功能来发挥其抗炎作用。实验结果有力地支持了PPAR激动剂在哮喘治疗中的潜在临床益处。我们回顾了当前的文献,强调了PPAR在哮喘发病机制中的关键作用及其激动剂的治疗潜力。通过进一步的研究和严格的临床研究,PPAR可能成为这种疾病有吸引力的治疗靶点。