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白三烯、脂氧素和氧代二十碳烯酸受体的最新进展:IUPHAR综述7

Update on leukotriene, lipoxin and oxoeicosanoid receptors: IUPHAR Review 7.

作者信息

Bäck Magnus, Powell William S, Dahlén Sven-Erik, Drazen Jeffrey M, Evans Jilly F, Serhan Charles N, Shimizu Takao, Yokomizo Takehiko, Rovati G Enrico

机构信息

Nomenclature Subcommittee for Leukotriene Receptors, International Union of Basic and Clinical Pharmacology, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.

出版信息

Br J Pharmacol. 2014 Aug;171(15):3551-74. doi: 10.1111/bph.12665. Epub 2014 Jul 12.

Abstract

The endogenous ligands for the LT, lipoxin (LX) and oxoeicosanoid receptors are bioactive products produced by the action of the lipoxygenase family of enzymes. The LT receptors BLT1 and BLT2 , are activated by LTB4 and the CysLT1 and CysLT2 receptors are activated by the cysteinyl-LTs, whereas oxoeicosanoids exert their action through the OXE receptor. In contrast to these pro-inflammatory mediators, LXA4 transduces responses associated with the resolution of inflammation through the receptor FPR2/ALX (ALX/FPR2). The aim of the present review is to give a state of the field on these receptors, with focus on recent important findings. For example, BLT1 receptor signalling in cancer and the dual role of the BLT2 receptor in pro- and anti-inflammatory actions have added more complexity to lipid mediator signalling. Furthermore, a cross-talk between the CysLT and P2Y receptor systems has been described, and also the presence of novel receptors for cysteinyl-LTs, such as GPR17 and GPR99. Finally, lipoxygenase metabolites derived from ω-3 essential polyunsaturated acids, the resolvins, activate the receptors GPR32 and ChemR23. In conclusion, the receptors for the lipoxygenase products make up a sophisticated and tightly controlled system of endogenous pro- and anti-inflammatory signalling in physiology and pathology.

摘要

白三烯(LT)、脂氧素(LX)和氧代二十碳烯酸受体的内源性配体是脂氧合酶家族酶作用产生的生物活性产物。LT受体BLT1和BLT2由白三烯B4(LTB4)激活,半胱氨酰白三烯受体CysLT1和CysLT2由半胱氨酰白三烯激活,而氧代二十碳烯酸则通过OXE受体发挥作用。与这些促炎介质不同,脂氧素A4(LXA4)通过受体FPR2/ALX(ALX/FPR2)转导与炎症消退相关的反应。本综述的目的是介绍这些受体的研究现状,重点关注近期的重要发现。例如,癌症中的BLT1受体信号传导以及BLT2受体在促炎和抗炎作用中的双重作用增加了脂质介质信号传导的复杂性。此外,已经描述了半胱氨酰白三烯(CysLT)和P2Y受体系统之间的相互作用,以及半胱氨酰白三烯的新型受体如GPR17和GPR99的存在。最后,源自ω-3必需多不饱和酸的脂氧合酶代谢产物——消退素,激活受体GPR32和ChemR23。总之,脂氧合酶产物的受体在生理和病理状态下构成了一个复杂且严格调控的内源性促炎和抗炎信号系统。

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