PPARγ and the Innate Immune System Mediate the Resolution of Inflammation.
PPARγ and the Innate Immune System Mediate the Resolution of Inflammation.
复制标题
DOI：
10.1155/2015/549691
复制
发表时间：
2015
期刊：
影响因子：
2.9
通讯作者：
Phipps RP
中科院分区：
文献类型：
--
作者：
Croasdell A;Duffney PF;Kim N;Lacy SH;Sime PJ;Phipps RP
炎症的消退是一个积极的动态过程，在很大程度上是由先天免疫系统介导的。分辨率不仅代表抗炎作用的增加，而且还代表免疫细胞功能的范式转变，以恢复体内平衡。PPARγ是一种配体激活的转录因子，其抗炎作用已被研究了很长时间，但新出现的文献正在研究PPARγ及其配体（包括噻唑烷二酮类、前列腺素和齐墩果酸）在所有溶解阶段的作用。PPARγ可以通过中性粒细胞、血小板和巨噬细胞从促炎介质转变为抗炎介质。PPARγ及其配体进一步调节血小板和中性粒细胞功能，减少运输，促进中性粒细胞凋亡，并阻止血小板-白细胞相互作用。PPARγ改变巨噬细胞运输，增加efferocytosis和吞噬作用，并促进替代M2巨噬细胞活化。这种受体在适应性免疫反应中也有作用，特别是对B细胞。在动物模型中，这些作用有助于减轻多种疾病状态，包括慢性阻塞性肺病、结肠炎、阿尔茨海默病和肥胖。最后，新的专门的促分解介质-在分解中起关键作用的二十烷类物质-可能通过PPARγ调节来促进分解，为该受体提供了另一个令人兴奋的治疗潜力领域。
The resolution of inflammation is an active and dynamic process, mediated in large part by the innate immune system. Resolution represents not only an increase in anti-inflammatory actions, but also a paradigm shift in immune cell function to restore homeostasis. PPARγ, a ligand activated transcription factor, has long been studied for its anti-inflammatory actions, but an emerging body of literature is investigating the role of PPARγ and its ligands (including thiazolidinediones, prostaglandins, and oleanolic acids) in all phases of resolution. PPARγ can shift production from pro- to anti-inflammatory mediators by neutrophils, platelets, and macrophages. PPARγ and its ligands further modulate platelet and neutrophil function, decreasing trafficking, promoting neutrophil apoptosis, and preventing platelet-leukocyte interactions. PPARγ alters macrophage trafficking, increases efferocytosis and phagocytosis, and promotes alternative M2 macrophage activation. There are also roles for this receptor in the adaptive immune response, particularly regarding B cells. These effects contribute towards the attenuation of multiple disease states, including COPD, colitis, Alzheimer's disease, and obesity in animal models. Finally, novel specialized proresolving mediators—eicosanoids with critical roles in resolution—may act through PPARγ modulation to promote resolution, providing another exciting area of therapeutic potential for this receptor.