Role of metabolic reprogramming in pro-inflammatory cytokine secretion from LPS or silica-activated macrophages.
Role of metabolic reprogramming in pro-inflammatory cytokine secretion from LPS or silica-activated macrophages.
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代谢重编程在LPS或二氧化硅活化巨噬细胞促炎细胞因子分泌中的作用。
DOI：
10.3389/fimmu.2022.936167
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
在肺中，巨噬细胞构成了抵抗病原体和异物的第一道防线，并在维持组织稳态方面发挥着重要作用。活化的巨噬细胞显示出改变的免疫代谢和控制免疫效应机制的代谢变化，例如表征其经典（M1）或替代（M2）活化的细胞因子分泌。脂多糖（LPS）刺激的巨噬细胞表现出糖酵解增强，琥珀酸脱氢酶（SDH）受阻，白细胞介素-1 β（IL-1β）和肿瘤坏死因子-α（TNF-α）分泌增加。在LPS刺激的巨噬细胞中使用2-脱氧葡萄糖抑制糖酵解抑制IL-1β分泌，但不抑制TNF-α，表明代谢途径特异性决定细胞因子产生。与LPS相反，在巨噬细胞中由无机颗粒（例如二氧化硅）诱导的免疫代谢反应的性质、其对细胞因子特异性的贡献以及疾病发病机制尚不清楚。二氧化硅刺激的巨噬细胞激活模式识别受体（PRR）和NLRP 3炎性体，并释放IL-1β、TNF-α和干扰素，这些是矽肺发病机制的关键介质。与细菌相反，二氧化硅颗粒不能降解，并且持续的巨噬细胞活化导致NADPH氧化酶（Phox）活化和线粒体活性氧（ROS）产生增加，最终导致巨噬细胞死亡和使炎症持续的二氧化硅颗粒的释放。在这篇手稿中，我们回顾了二氧化硅对巨噬细胞线粒体呼吸和中心碳代谢的影响，决定细胞因子的规格负责在肺部持续的炎症反应。
In the lungs, macrophages constitute the first line of defense against pathogens and foreign bodies and play a fundamental role in maintaining tissue homeostasis. Activated macrophages show altered immunometabolism and metabolic changes governing immune effector mechanisms, such as cytokine secretion characterizing their classic (M1) or alternative (M2) activation. Lipopolysaccharide (LPS)-stimulated macrophages demonstrate enhanced glycolysis, blocked succinate dehydrogenase (SDH), and increased secretion of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Glycolysis suppression using 2 deoxyglucose in LPS-stimulated macrophages inhibits IL-1β secretion, but not TNF-α, indicating metabolic pathway specificity that determines cytokine production. In contrast to LPS, the nature of the immunometabolic responses induced by non-organic particles, such as silica, in macrophages, its contribution to cytokine specification, and disease pathogenesis are not well understood. Silica-stimulated macrophages activate pattern recognition receptors (PRRs) and NLRP3 inflammasome and release IL-1β, TNF-α, and interferons, which are the key mediators of silicosis pathogenesis. In contrast to bacteria, silica particles cannot be degraded, and the persistent macrophage activation results in an increased NADPH oxidase (Phox) activation and mitochondrial reactive oxygen species (ROS) production, ultimately leading to macrophage death and release of silica particles that perpetuate inflammation. In this manuscript, we reviewed the effects of silica on macrophage mitochondrial respiration and central carbon metabolism determining cytokine specification responsible for the sustained inflammatory responses in the lungs.
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影响因子：
7.3
作者：
Dominguez-Gutierrez PR;Kusmartsev S;Canales BK;Khan SR
通讯作者：
Khan SR
影响因子：
4.3
作者：
Becerra-Diaz, Mireya;Lerner, Andrew D.;Yu, Diana H.;Thiboutot, Jeffrey P.;Liu, Mark C.;Yarmus, Lonny B.;Bose, Sonali;Heller, Nicola M.
通讯作者：
Heller, Nicola M.
影响因子：
3.8
作者：
Anderson SE;Shane H;Long C;Marrocco A;Lukomska E;Roberts JR;Marshall N;Fedan JS
通讯作者：
Fedan JS
影响因子：
2.1
作者：
Berg, IA;Filatova, LV;Ivanovsky, RN
通讯作者：
Ivanovsky, RN
影响因子：
3.7
作者：
Di Giuseppe M;Gambelli F;Hoyle GW;Lungarella G;Studer SM;Richards T;Yousem S;McCurry K;Dauber J;Kaminski N;Leikauf G;Ortiz LA
通讯作者：
Ortiz LA