Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, People's Republic of China.
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, People's Republic of China.
Pharmacol Res. 2020 Aug;158:104857. doi: 10.1016/j.phrs.2020.104857. Epub 2020 May 18.
Leukotriene B4 (LTB4) is a major type of lipid mediator that is rapidly generated from arachidonic acid through sequential action of 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTA4 hydrolase (LTA4H) in response to various stimuli. LTB4 is well known to be a chemoattractant for leukocytes, particularly neutrophils, via interaction with its high-affinity receptor BLT1. Extensive attention has been paid to the role of the LTB4-BLT1 axis in acute and chronic inflammatory diseases, such as infectious diseases, allergy, autoimmune diseases, and metabolic disease via mediating recruitment and/or activation of different types of inflammatory cells depending on different stages or the nature of inflammatory response. Recent studies also demonstrated that LTB4 acts on non-immune cells via BLT1 to initiate and/or amplify pathological inflammation in various tissues. In addition, emerging evidence reveals a complex role of the LTB4-BLT1 axis in cancer, either tumor-inhibitory or tumor-promoting, depending on the different target cells. In this review, we summarize both established understanding and the most recent progress in our knowledge about the LTB4-BLT1 axis in host defense, inflammatory diseases and cancer.
白三烯 B4（LTB4）是一种主要的脂质介质，可通过 5-脂氧合酶（5-LO）、5-脂氧合酶激活蛋白（FLAP）和 LTA4 水解酶（LTA4H）在各种刺激下从花生四烯酸中快速生成。LTB4 是众所周知的白细胞，特别是中性粒细胞的趋化因子，通过与其高亲和力受体 BLT1 相互作用。大量关注集中在 LTB4-BLT1 轴在急性和慢性炎症性疾病中的作用，如传染病、过敏、自身免疫性疾病和代谢性疾病，通过根据炎症反应的不同阶段或性质调节不同类型的炎症细胞的募集和/或激活。最近的研究还表明，LTB4 通过 BLT1 作用于非免疫细胞，在各种组织中引发和/或放大病理性炎症。此外，新出现的证据揭示了 LTB4-BLT1 轴在癌症中的复杂作用，无论是肿瘤抑制还是肿瘤促进，这取决于不同的靶细胞。在这篇综述中，我们总结了 LTB4-BLT1 轴在宿主防御、炎症性疾病和癌症中的既有认识和最新进展。
