A novel anti-inflammatory and pro-resolving role for resolvin D1 in acute cigarette smoke-induced lung inflammation.
A novel anti-inflammatory and pro-resolving role for resolvin D1 in acute cigarette smoke-induced lung inflammation.
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DOI：
10.1371/journal.pone.0058258
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sime PJ
中科院分区：
文献类型：
--
作者：
Hsiao HM;Sapinoro RE;Thatcher TH;Croasdell A;Levy EP;Fulton RA;Olsen KC;Pollock SJ;Serhan CN;Phipps RP;Sime PJ
香烟烟雾是一种严重的促炎刺激物，可导致急性肺损伤和慢性肺病，包括COPD（肺气肿和慢性支气管炎）。直到最近，人们认为炎症的消退是一个被动的过程，一旦炎症刺激被去除就会发生。现在认识到，炎症的消退是由专门的脂质介质介导的生物活性过程，并且正常的稳态由促炎和促消退途径之间的平衡维持。这些新的小脂质介质，包括resolvins、protectins和maresins，是主要来源于膳食ω-3和ω-6多不饱和脂肪酸（PUFA）的生物活性产物。我们假设，resolvin D1（RvD 1）在香烟烟雾诱导的肺部炎症模型中具有有效的抗炎和促消退作用。在体外用IL-1β或香烟烟雾提取物与RvD 1组合处理原代人肺成纤维细胞、小气道上皮细胞和血单核细胞，测量促炎介质的产生。将小鼠暴露于稀释的主流香烟烟雾中，并与烟雾同时或在戒烟后用RvD 1治疗。评估了对肺部炎症和肺巨噬细胞群的影响。RvD 1以剂量依赖性方式抑制原代人细胞产生促炎介质。用RvD 1同时暴露于香烟烟雾的小鼠的治疗显著减少了嗜酸性肺部炎症和促炎细胞因子的产生，同时上调了抗炎细胞因子IL-10。RvD 1促进交替激活（M2）巨噬细胞的分化和中性粒细胞增多。RvD 1在最后一次烟雾暴露后给药时也加速了肺部炎症的消退。RvD 1在暴露于香烟烟雾的细胞和小鼠中具有有效的抗炎和促消退作用。Resolvins作为一种新的治疗方法具有很强的潜力，以解决由烟雾和肺毒物引起的肺损伤。
Cigarette smoke is a profound pro-inflammatory stimulus that contributes to acute lung injuries and to chronic lung disease including COPD (emphysema and chronic bronchitis). Until recently, it was assumed that resolution of inflammation was a passive process that occurred once the inflammatory stimulus was removed. It is now recognized that resolution of inflammation is a bioactive process, mediated by specialized lipid mediators, and that normal homeostasis is maintained by a balance between pro-inflammatory and pro-resolving pathways. These novel small lipid mediators, including the resolvins, protectins and maresins, are bioactive products mainly derived from dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFA). We hypothesize that resolvin D1 (RvD1) has potent anti-inflammatory and pro-resolving effects in a model of cigarette smoke-induced lung inflammation. Primary human lung fibroblasts, small airway epithelial cells and blood monocytes were treated with IL-1β or cigarette smoke extract in combination with RvD1 in vitro, production of pro-inflammatory mediators was measured. Mice were exposed to dilute mainstream cigarette smoke and treated with RvD1 either concurrently with smoke or after smoking cessation. The effects on lung inflammation and lung macrophage populations were assessed. RvD1 suppressed production of pro-inflammatory mediators by primary human cells in a dose-dependent manner. Treatment of mice with RvD1 concurrently with cigarette smoke exposure significantly reduced neutrophilic lung inflammation and production of pro-inflammatory cytokines, while upregulating the anti-inflammatory cytokine IL-10. RvD1 promoted differentiation of alternatively activated (M2) macrophages and neutrophil efferocytosis. RvD1 also accelerated the resolution of lung inflammation when given after the final smoke exposure. RvD1 has potent anti-inflammatory and pro-resolving effects in cells and mice exposed to cigarette smoke. Resolvins have strong potential as a novel therapeutic approach to resolve lung injury caused by smoke and pulmonary toxicants.
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DOI：
10.1164/ajrccm/139.6.1395
发表时间：
1989-06-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
ARM, JP;HORTON, CE;LEE, TH
通讯作者：
LEE, TH
影响因子：
4.3
作者：
Joo, Min J.;Au, David H.;Lee, Todd A.
通讯作者：
Lee, Todd A.
影响因子：
6.6
作者：
Caito, Samuel;Yang, Se-Ran;Rahman, Irfan
通讯作者：
Rahman, Irfan
影响因子：
2.1
作者：
Burgess, JL;Nanson, CJ;Lantz, RC
通讯作者：
Lantz, RC
影响因子：
2.5
作者：
Ogawa Y;Duru EA;Ameredes BT
通讯作者：
Ameredes BT