Fu Ting, Mohan Muthukumar, Brennan Eoin P, Woodman Owen L, Godson Catherine, Kantharidis Phillip, Ritchie Rebecca H, Qin Cheng Xue
Heart Failure Pharmacology, Baker Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia.
ACS Pharmacol Transl Sci. 2020 Jan 17;3(1):43-55. doi: 10.1021/acsptsci.9b00097. eCollection 2020 Feb 14.
Several studies have shown that failure to resolve inflammation may contribute to the progression of many chronic inflammatory disorders. It has been suggested targeting the resolution of inflammation might be a novel therapeutic approach for chronic inflammatory diseases, including inflammatory bowel disease, diabetic complications, and cardiometabolic disease. Lipoxins [LXs] are a class of endogenously generated mediators that promote the resolution of inflammation. Biological actions of LXs include inhibition of neutrophil infiltration, promotion of macrophage polarization, increase of macrophage efferocytosis, and restoration of tissue homeostasis. Recently, several studies have demonstrated that LXs and synthetic analogues protect tissues from acute and chronic inflammation. The mechanism includes down-regulation of pro-inflammatory cytokines and chemokines (e.g., interleukin-1β and tumor necrosis factor-α), inhibition of the activation of the master pro-inflammatory pathway (e.g., nuclear factor κ-light-chain-enhancer of activated B cells pathway) and increased release of the pro-resolving cytokines (e.g., interleukin-10). Three generations of LXs analogues are well described in the literature, and more recently a fourth generation has been generated that appears to show enhanced potency. In this review, we will briefly discuss the potential therapeutic opportunity provided by lipoxin A as a novel approach to treat chronic inflammatory disorders, focusing on cardiometabolic disease and the current drug development in this area.
多项研究表明，炎症未能得到缓解可能会促使许多慢性炎症性疾病的进展。有人提出，针对炎症的消退可能是治疗慢性炎症性疾病的一种新的治疗方法，这些疾病包括炎症性肠病、糖尿病并发症和心脏代谢疾病。脂氧素[LXs]是一类内源性产生的介质，可促进炎症的消退。LXs的生物学作用包括抑制中性粒细胞浸润、促进巨噬细胞极化、增加巨噬细胞的胞葬作用以及恢复组织稳态。最近，多项研究表明，LXs及其合成类似物可保护组织免受急性和慢性炎症的影响。其机制包括下调促炎细胞因子和趋化因子（如白细胞介素-1β和肿瘤坏死因子-α）、抑制主要促炎途径（如活化B细胞核因子κ轻链增强子途径）的激活以及增加促消退细胞因子（如白细胞介素-10）的释放。文献中对三代LXs类似物已有详尽描述，最近又产生了第四代，其效力似乎有所增强。在本综述中，我们将简要讨论脂氧素A作为治疗慢性炎症性疾病的一种新方法所提供的潜在治疗机会，重点关注心脏代谢疾病以及该领域目前的药物研发情况。
