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Therapeutic Potential of Lipoxin A4 in Chronic Inflammation: Focus on Cardiometabolic Disease
ACS Pharmacology & Translational Science Pub Date : 2020-02-03 , DOI: 10.1021/acsptsci.9b00097
Ting Fu 1, 2 , Muthukumar Mohan 3 , Eoin P. Brennan 4 , Owen L. Woodman 1 , Catherine Godson 4 , Phillip Kantharidis 3 , Rebecca H. Ritchie 1, 2, 3, 5 , Cheng Xue Qin 1, 2, 3
Affiliation  

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 A4 as a novel approach to treat chronic inflammatory disorders, focusing on cardiometabolic disease and the current drug development in this area.

中文翻译:

Lipoxin A 4在慢性炎症中的治疗潜力:重点研究心脏代谢疾病

几项研究表明,无法解决炎症可能导致许多慢性炎症性疾病的发展。已经提出,针对炎症的解决可能是针对慢性炎性疾病的新型治疗方法,包括炎性肠病,糖尿病并发症和心脏代谢性疾病。脂蛋白[LXs]是一类内源性产生的介质,可促进炎症的消退。LX的生物学作用包括抑制嗜中性白细胞的浸润,促进巨噬细胞极化,增加巨噬细胞的胞吞作用和组织稳态的恢复。最近,一些研究表明LX和合成类似物可保护组织免于急性和慢性炎症。该机制包括下调促炎细胞因子和趋化因子(例如白介素-1β和肿瘤坏死因子-α),抑制主要促炎途径的激活(例如核因子κ-轻链增强子)激活的B细胞途径)和促分解细胞因子(例如白介素10)的释放增加。在文献中已经很好地描述了三代LXs类似物,并且最近已经产生了第四代,其似乎显示出增强的效力。在这篇综述中,我们将简要讨论脂蛋白A提供的潜在治疗机会 核因子κ-轻链增强的B细胞活化途径)和促分解细胞因子(例如白介素10)的释放增加。在文献中已经很好地描述了三代LXs类似物,并且最近已经产生了第四代,其似乎显示出增强的效力。在这篇综述中,我们将简要讨论脂蛋白A提供的潜在治疗机会 核因子κ-轻链增强的B细胞活化途径)和促分解细胞因子(例如白介素10)的释放增加。在文献中已经很好地描述了三代LXs类似物,并且最近已经产生了第四代,其似乎显示出增强的效力。在这篇综述中,我们将简要讨论脂蛋白A提供的潜在治疗机会4作为治疗慢性炎性疾病的新方法,重点关注心脏代谢疾病和该领域当前的药物开发。
更新日期:2020-02-03
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