Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13
Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13
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姜黄素通过分泌 IL-4 和/或 IL-13 诱导 M2 巨噬细胞极化
DOI：
10.1016/j.yjmcc.2015.04.025
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发表时间：
2015-08-01
影响因子：
5
通讯作者：
Yuan, Zuyi
中科院分区：
文献类型：
--
作者：
Gao, Shanshan;Zhou, Juan;Yuan, Zuyi
目的：探讨姜黄素促进巨噬细胞M2表型极化的潜在机制及其在实验性自身免疫性心肌炎（EAM）保护作用中的作用。方法和结果：经典的M2标志物，包括巨噬细胞甘露糖受体（MMR），姜黄素处理的Raw 264.7巨噬细胞中，精氨酸酶-1（Arg-1）和过氧化物酶体增殖物激活受体-γ（PPAR-gamma）上调。姜黄素增加白细胞介素-4（IL-4）和白细胞介素-13（IL-13）的mRNA表达和蛋白分泌。姜黄素显著增加STAT 6磷酸化。STAT 6抑制剂来氟米特和IL-4和/或IL-13中和抗体拮抗姜黄素对Raw 264.7细胞中MMR、Arg-1和PPAR-gamma的诱导。在体内，使用6周龄雄性刘易斯大鼠诱导EAM，并在肌球蛋白注射后口服姜黄素或玉米油3周。姜黄素治疗后左室短轴缩短率（LVFS）、射血分数（EF）、左室收缩末期内径（LVEDs）和心率（HR）等心功能指标均明显改善。姜黄素还减少炎性细胞浸润和心肌白细胞介素-1 β（IL-1 β）和诱导型一氧化氮合酶（iNOS）的mRNA水平。姜黄素可显著上调心肌MMR和Arg-1的mRNA水平。免疫荧光检测显示，姜黄素处理组心肌组织中CD 68（+）MMR+和CD 68（+）Arg-1（+）双阳性巨噬细胞数量明显高于对照组。结论：姜黄素可通过分泌IL-4和/或IL-13诱导巨噬细胞M2极化。姜黄素通过减少炎性巨噬细胞浸润和使M0和M1巨噬细胞极化为M2表型来改善EAM。(C)2015爱思唯尔有限公司版权所有。
Aims: To address the underlying mechanisms by which curcumin facilitates M2 phenotype polarization of macrophages and its roles in the protective effects during experimental autoimmune myocarditis (EAM).Methods and results: The expression of classic M2 markers, including macrophage mannose receptor (MMR), arginase-1 (Arg-1) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) was upregulated in curcumin-treated Raw264.7 macrophages. Curcumin increased interleukin-4 (IL-4) and interleukin-13 (IL-13) mRNA expression and protein secretion. Curcumin notably increased STAT6 phosphorylation. Leflunomide, a STAT6 inhibitor, and IL-4 and/or IL-13 neutralizing antibodies antagonized the induction of MMR, Arg-1 and PPAR-gamma by curcumin in Raw264.7 cells. In vivo, 6-week old male Lewis rats were used to induce EAM and orally administrated with curcumin or corn oil for 3 weeks after myosin injection. Cardiac functional parameters, including left ventricular fractional shortening (LVFS), ejection fraction (EF), left ventricular end-systolic diameter (LVEDs) and heart rate (HR) were significantly improved by curcumin treatment. Curcumin also reduced the inflammatory cell infiltration and myocardial mRNA levels of interleukin-1 beta (IL-1 beta) and inducible nitric oxide synthase (iNOS). Meanwhile, the myocardial mRNA levels of MMR and Arg-1 were markedly up-regulated by curcumin. Immunofluorescence assay showed that the number of CD68(+) MMR+ and CD68(+) Arg-1(+) double positive macrophages in curcumin-treated myocardial tissue was significantly higher than untreated control. The number of CD68(+) iNOS(+) double positive macrophages was increased obviously in EAM group, but decreased markedly by curcumin treatment.Conclusions: Taken together, these results show that curcumin induces macrophage M2 polarization by secretion of IL-4 and/or IL-13. Curcumin ameliorates EAM by reducing infiltration inflammatory macrophages and by polarizing M0 and M1 macrophages to M2 phenotype. (C) 2015 Elsevier Ltd. All rights reserved.