Romano Mario
Department of Biomedical Sciences, Aging Research Center, Ce.S.I., Gabriele D'Annunzio University Foundation, Chieti, Italy.
ScientificWorldJournal. 2010 Jun 2;10:1048-64. doi: 10.1100/tsw.2010.113.
Lipoxins and their 15 epimers, aspirin triggered lipoxins (ATL), are eicosanoids derived from sequential lipoxygenase (LO) metabolism of arachidonic acid. The main routes of lipoxin biosynthesis involve cooperation between 15- and 5-LO, and between 12- and 5-LO. ATL are generated by interactions between 5-LO and aspirin-acetylated cyclooxygenase-2. Cellular models recapitulating these interactions involve leukocytes, platelets, vascular endothelium, and epithelium. To circumvent rapid lipoxin and ATL metabolism and inactivation, stable analogs, bearing potent and long-lasting biological activity, have been synthesized. Some of these analogs displayed therapeutic potential by showing strong anti-inflammatory activity in a number of animal models of disease, including reperfusion injury; arthritis; gastrointestinal, renal, respiratory, and vascular inflammatory disorders; eye damage; periodontitis; and selected infectious diseases. Counter-regulatory signaling by lipoxin A4 and 15-epi-lipoxin A4 is triggered by the activation of a seven-transmembrane domain receptor, termed FPR2/ALX, which is highly expressed in myeloid cells and has been recognized as a main anti-inflammatory receptor.
脂氧素及其15个差向异构体，即阿司匹林触发脂氧素（ATL），是由花生四烯酸经脂氧合酶（LO）顺序代谢产生的类二十烷酸。脂氧素生物合成的主要途径涉及15-脂氧合酶和5-脂氧合酶之间以及12-脂氧合酶和5-脂氧合酶之间的协同作用。ATL是由5-脂氧合酶与阿司匹林乙酰化的环氧化酶-2相互作用产生的。概括这些相互作用的细胞模型包括白细胞、血小板、血管内皮细胞和上皮细胞。为了避免脂氧素和ATL的快速代谢和失活，已合成了具有强大而持久生物活性的稳定类似物。其中一些类似物在包括再灌注损伤、关节炎、胃肠道、肾脏、呼吸道和血管炎症性疾病、眼损伤、牙周炎以及某些传染病在内的多种疾病动物模型中显示出强大的抗炎活性，从而展现出治疗潜力。脂氧素A4和15-表脂氧素A4的反向调节信号是由一种七跨膜结构域受体（称为FPR2/ALX）的激活触发的，该受体在髓样细胞中高度表达，并且已被公认为主要的抗炎受体。
