Endocannabinoids alleviate proinflammatory conditions by modulating innate immune response in muller glia during inflammation
Endocannabinoids alleviate proinflammatory conditions by modulating innate immune response in muller glia during inflammation
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DOI：
10.1002/glia.22380
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发表时间：
2012-11-01
期刊：
影响因子：
6.2
通讯作者：
Chatterjee, Nivedita
中科院分区：
文献类型：
--
作者：
Krishnan, Gopinath;Chatterjee, Nivedita
穆勒细胞在视网膜的炎症状态中起着重要作用。它们是视网膜先天免疫反应的一部分。内源性大麻素系统在外周免疫系统和中枢神经系统中都起到免疫调节剂的作用。我们假设外源性内源性大麻素在视网膜的神经保护能力部分是通过Muller神经胶质细胞介导的。这项研究报告说，暴露于激活的但不是静止的原代人类Muller胶质细胞中的内源性大麻素抑制了几种促炎细胞因子的产生，同时提高了抗炎介质的水平。内源性大麻素通过丝裂原活化蛋白激酶(MAPK)家族在多个信号阶段调节活化的Muller胶质细胞中细胞因子的产生。花生胺(AEA)通过MKP-1调控MAPK的磷酸化。AEA和2-花生四烯酸甘油(2-AG)均抑制转录因子NF-kappa B，增加调节蛋白IL1-R相关蛋白结合蛋白1。内源性大麻素还促进激活的Muller细胞中Tristetraprolin的表达，这可能与影响富含AU的促炎细胞因子的mRNA有关。我们证明，外源性应用AEA和2-AG通过创造抗炎环境来帮助炎症条件下的视网膜细胞存活。因此，内源性大麻素或合成大麻素治疗可能会协调分子开关，以偏向先天免疫系统，例如，促炎和抗炎细胞因子生成的平衡创造了一个生存环境。(C)2012年威利期刊公司。
Muller cells play a prominent role in inflammatory conditions of the retina. They are part of the retinal innate immune response. The endocannabinoid system functions as an immune modulator in both the peripheral immune system as well as the central nervous system. We hypothesized that the neuroprotective ability of exogenous endocannabinoids in the retina is partially mediated through Muller glia. This study reports that exposure to endocannabinoids in activated but not resting primary human Muller glia inhibit production of several proinflammatory cytokines, while elevating anti-inflammatory mediators. Cytokine generation in activated Muller glia is regulated by endocannabinoids through the mitogen-activated protein kinase (MAPK) family at multiple signaling stages. Anandamide (AEA) acts to control MAPK phosphorylation through MKP-1. Both AEA and 2-arachidonoylglycerol (2-AG) inhibit the transcription factor NF-kappa B and increases the regulatory protein, IL1-R-associated kinase 1-binding protein 1. Endocannabinoids also increase expression of Tristetraprolin in activated Muller cells, which is implicated in affecting AU-rich proinflammatory cytokine mRNA. We demonstrate that exogenous application of AEA and 2-AG aid in retinal cell survival under inflammatory conditions by creating an anti-inflammatory milieu. Endocannabinoids or synthetic cannabinoid therapy may therefore orchestrate a molecular switch to bias the innate immune system suchthat the balance of pro- and anti-inflammatory cytokine generation creates a prosurvival milieu. (c) 2012 Wiley Periodicals, Inc.