Oguma Tsuyoshi, Asano Koichiro, Ishizaka Akitoshi
Department of Medicine, Keio University School of Medicine,Tokyo, Japan.
Allergol Int. 2008 Dec;57(4):307-12. doi: 10.2332/allergolint.08-RAI-0033. Epub 2008 Nov 1.
Prostaglandin D(2) (PGD(2)) is one of the most abundant lipid mediators present in the airways of asthmatics. However, little was known of the role it plays in the pathophysiology of asthma, until the identification of DP (DP1, PTGDR) and CRTH2 (DP2), two PGD(2)-specific transmembrane receptors with different distribution and intracellular signaling. Pharmacological tools, such as receptor-specific agonists and antagonists, and genetically-engineered mice, which lack either DP or CRTH2, have helped understand the complex effects of PGD(2) in allergic inflammation of the airways. Furthermore, genetic association studies have shown a positive linkage of the genetic polymorphisms in DP and CRTH2, with asthma phenotypes from specific ethnic backgrounds, further highlighting the importance of PGD(2) and its receptors in the pathophysiology of asthma.
前列腺素D2(PGD2)是哮喘患者气道中含量最丰富的脂质介质之一。然而,在确定DP(DP1,PTGDR)和CRTH2(DP2)这两种分布和细胞内信号传导不同的PGD2特异性跨膜受体之前,人们对其在哮喘病理生理学中所起的作用知之甚少。受体特异性激动剂和拮抗剂等药理学工具以及缺乏DP或CRTH2的基因工程小鼠,有助于了解PGD2在气道过敏性炎症中的复杂作用。此外,基因关联研究表明,DP和CRTH2中的基因多态性与特定种族背景的哮喘表型呈正相关,进一步凸显了PGD2及其受体在哮喘病理生理学中的重要性。