Monocytes primed with GTS-21/α7 nAChR (nicotinic acetylcholine receptor) agonist develop anti-inflammatory memory
Monocytes primed with GTS-21/α7 nAChR (nicotinic acetylcholine receptor) agonist develop anti-inflammatory memory
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用 GTS-21/α7 nAChR（烟碱乙酰胆碱受体）激动剂引发的单核细胞可形成抗炎记忆
DOI：
10.1093/qjmed/hcx014
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Xiao Su
中科院分区：
文献类型：
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作者：
Xi Yang;Caiqi Zhao;Xiu Chen;Lubin Jiang;Xiao Su
背景：神经系统可以微调免疫系统，特别是单核细胞/巨噬细胞的促炎或抗炎反应。为了维持免疫稳态，单核细胞/巨噬细胞应该被α7 nAChR激动剂启动以建立抗炎记忆。目的：研究α7 nAChR的激活是否会在体内脾单核细胞和体外J774单核细胞中引发抗炎记忆。设计：实验室研究。方法：野生型小鼠 接受静脉注射GTS-21后4或12小时处死。分离脾细胞并用LPS刺激4小时，通过流式细胞术检测Ly6ChiTNF-α+单核细胞。在体外研究中，J774单核细胞接受GTS-21引发，洗掉GTS-21并静置，然后用TLR配体刺激。测量TNF-α蛋白和Tnfα、Il1β和il6mRNA以评估抗炎反应。在 GTS-21 引发的单核细胞中测量 H3K9ac、H4K5ac、H4K8ac、Acetyl-CBP、CBP（CREB 结合蛋白）、PCAF（P300/CBP 相关因子）和 Acetyl-NF-kB 水平。 结果：GTS-21 激活 α7 nAChR 抑制脾脏中 TNF-α 的产生 Ly6嵌合细胞。如果在体外用LPS刺激，体内GTS-21引发的脾Ly6嵌合细胞会传递抗炎特性。用 GTS-21 引发的 J774 单核细胞对 LPS (TLR4)、Poly:IC (TLR3) 和 R848 (TLR7/8) 配体产生抗炎特性。在 GTS-21 引发的单核细胞中，清洗和静置 4 小时后，H3K9ac、H4K5ac、H4K8ac、乙酰基-CBP、CBP、PCAF 和乙酰基-NF-kB 减少。在洗涤和静置后 4 小时，LPS 刺激的 GTS-21 引发的 J774 单核细胞的核提取物中，PCAF、乙酰基-NF-kB、p-NF-kB 和 p-STAT3 减少。结论：经 α7 nAChR 激动剂引发的单核细胞产生抗炎记忆。
Background:The neural system can finely tune immune system, especially pro- or anti-inflammatory responses of monocytes/macrophages. To maintain immune homeostasis, monocytes/macrophages are supposed to be primed by α7 nAChR agonist to establish anti-inflammatory memory.Aim:To study whether activation of α7 nAChR would elicit anti-inflammatory memory in splenic monocytesin vivoand J774 monocytesin vitro.Design:Laboratory study.Methods:The wildtype mice were sacrificed 4 or 12 h after receiving intravenous injection of GTS-21. The splenocytes were isolated and stimulated with LPS for 4 h to detect Ly6ChiTNF-α+monocytes by flow cytometry. In thein vitrostudy, J774 monocytes received priming with GTS-21, washing GTS-21 out and resting, and thereafter stimulating with TLR ligands. The TNF-α protein andTnfα,Il1βandil6mRNAs were measured to evaluate anti-inflammatory responses. The H3K9ac, H4K5ac, H4K8ac, Acetyl-CBP, CBP (CREB-binding protein), PCAF (P300/CBP-associated factor) and Acetyl-NF-kB levels were measured in GTS-21-primed monocytes.Results:Activation of α7 nAChR by GTS-21 suppressed TNF-α production in splenic Ly6Chimonocytes.In vivo-GTS-21-primed splenic Ly6Chimonocytes passed on anti-inflammatory feature if stimulated with LPSin vitro. J774 monocytes primed with GTS-21 developed anti-inflammatory trait in response to LPS (TLR4), Poly:IC (TLR3) and R848 (TLR7/8) ligands. In GTS-21-primed monocytes, H3K9ac, H4K5ac, H4K8ac, Acetyl-CBP, CBP, PCAF and Acetyl-NF-kB were reduced 4 h after washing and resting. In the nuclear extract, PCAF, Acetyl-NF-kB, p-NF-kB and p-STAT3 were decreased in LPS-stimulated GTS-21 primed J774 monocytes 4 h after washing and resting.Conclusions:Monocytes primed by α7 nAChR agonist developed anti-inflammatory memory.