Anandamide attenuates Th-17 cell-mediated delayed-type hypersensitivity response by triggering IL-10 production and consequent microRNA induction.
Anandamide attenuates Th-17 cell-mediated delayed-type hypersensitivity response by triggering IL-10 production and consequent microRNA induction.
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DOI：
10.1371/journal.pone.0093954
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Nagarkatti M
中科院分区：
文献类型：
--
作者：
Jackson AR;Nagarkatti P;Nagarkatti M
内源性大麻素[内源性大麻素]是脂类信号分子，已被证明可以调节免疫功能。然而，它们在Th17细胞调节中的作用以前还没有研究过。在本研究中，我们以甲基化牛血清白蛋白[MBSA]诱导的C57BL/6小鼠迟发性超敏反应(DTH)反应为模型，以Th17细胞为媒介，检测内源性大麻素的抗炎作用。给小鼠注射内源性大麻酰胺[AEA]，可以显著减轻MBSA引起的炎症，包括足垫肿胀、细胞浸润和引流淋巴结[LN]中的细胞增殖。AEA可显著降低引流性LN中IL-17和干扰素-γ的产生，降低RoR-γt的表达，同时显著诱导引流的LN产生IL-10。IL-10在AEA诱导的DTH反应的缓解中起关键作用，因为IL-10的中和作用逆转了AEA的作用。接下来，我们分析了来自LN细胞的miRNA，发现609种miRNA中有100种在AEA处理的小鼠中与对照组相比有不同的调节。这些miRNAs中有几个是针对促炎介质的。有趣的是，这些miRNA中的许多也在IL-10体外处理LN细胞时上调。综上所述，目前的研究表明，AEA可能通过诱导IL-10来抑制Th-17细胞介导的DTH反应，而IL-10反过来又触发针对促炎途径的miRNA。
Endogenous cannabinoids [endocannabinoids] are lipid signaling molecules that have been shown to modulate immune functions. However, their role in the regulation of Th17 cells has not been studied previously. In the current study, we used methylated Bovine Serum Albumin [mBSA]-induced delayed type hypersensitivity [DTH] response in C57BL/6 mice, mediated by Th17 cells, as a model to test the anti-inflammatory effects of endocannabinoids. Administration of anandamide [AEA], a member of the endocannabinoid family, into mice resulted in significant mitigation of mBSA-induced inflammation, including foot pad swelling, cell infiltration, and cell proliferation in the draining lymph nodes [LN]. AEA treatment significantly reduced IL-17 and IFN-γ production, as well as decreased RORγt expression while causing significant induction of IL-10 in the draining LNs. IL-10 was critical for the AEA-induced mitigation of DTH response inasmuch as neutralization of IL-10 reversed the effects of AEA. We next analyzed miRNA from the LN cells and found that 100 out of 609 miRNA species were differentially regulated in AEA-treated mice when compared to controls. Several of these miRNAs targeted proinflammatory mediators. Interestingly, many of these miRNA were also upregulated upon in vitro treatment of LN cells with IL-10. Together, the current study demonstrates that AEA may suppress Th-17 cell–mediated DTH response by inducing IL-10 which in turn triggers miRNA that target proinflammatory pathways.
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DOI：
10.4049/jimmunol.1101235
发表时间：
2011-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lu TX;Hartner J;Lim EJ;Fabry V;Mingler MK;Cole ET;Orkin SH;Aronow BJ;Rothenberg ME
通讯作者：
Rothenberg ME
发育中的小鼠心脏的 microRNA 表达谱
影响因子：
5.4
作者：
Cao, Li;Kong, Li-Ping;Guo, Xi-Rong
通讯作者：
Guo, Xi-Rong
影响因子：
2.8
作者：
Kosaka, Shinichiro;Tamauchi, Hidekazu;Kitasato, Hidero
通讯作者：
Kitasato, Hidero
影响因子：
4.4
作者：
Lalor, Stephen J.;Dungan, Lara S.;Mills, Kingston H. G.
通讯作者：
Mills, Kingston H. G.
DOI：
10.1084/jem.170.6.2081
发表时间：
1989-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fiorentino DF;Bond MW;Mosmann TR
通讯作者：
Mosmann TR