Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.
Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.
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小胶质细胞响应 PAR-2 刺激而短暂释放早期神经营养因子并延迟释放炎症细胞因子
DOI：
10.1186/1742-2094-9-142
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发表时间：
2012-06-25
影响因子：
9.3
通讯作者：
Yuan HB
中科院分区：
文献类型：
--
作者：
Chen CW;Chen QB;Ouyang Q;Sun JH;Liu FT;Song DW;Yuan HB
激活的小胶质细胞对神经元产生有益和有害的影响，但控制这些不同反应的信号传导机制仍不清楚。我们证明，用PAR-2激动剂2-Furoyl-LIGRLO-NH 2处理小胶质细胞培养物，引起BDNF的早期瞬时释放，而持续的PAR-2刺激引起炎性细胞因子（IL-1β和TNF-α）和一氧化氮的延迟释放。在2-呋喃甲酰-LIGRLO-NH 2诱导的小胶质细胞活化的早期阶段（在1小时）收获的培养基（小胶质细胞条件培养基，MCM）对培养的神经元没有有害作用，而在晚期阶段（在72小时）收获的MCM促进DNA片段化和凋亡，如TUNEL和膜联蛋白/PI染色所示。PAR-2刺激的早期阶段的PAR-1的阻断增强BDNF的释放（11%，小但显著），而在晚期阶段（2-Furoyl-LIGRLO-NH 2添加后24小时）加入的PAR-1激动剂抑制细胞因子和NO的释放。激活的小胶质细胞的神经保护和神经毒性作用表现出不同的时间曲线，由PAR-1和PAR-2刺激调节。通过适时刺激和抑制小胶质细胞PAR-1和PAR-2受体，可能有助于神经元的恢复和修复。
Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.
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影响因子：
16.2
作者：
Smith, Patrice D.;Sun, Fang;Park, Kevin Kyungsuk;Cai, Bin;Wang, Chen;Kuwako, Kenichiro;Martinez-Carrasco, Irene;Connolly, Lauren;He, Zhigang
通讯作者：
He, Zhigang
影响因子：
4.4
作者：
Afkhami-Goli, Amir;Noorbakhsh, Farshid;Power, Christopher
通讯作者：
Power, Christopher
影响因子：
20.3
作者：
McEachron, Troy A.;Pawlinski, Rafal;Mackman, Nigel
通讯作者：
Mackman, Nigel
影响因子：
3.9
作者：
Park, Gyu Hwan;Jeon, Se Jin;Ko, Kwang Ho
通讯作者：
Ko, Kwang Ho
影响因子：
3.9
作者：
Park, Gyu Hwan;Jeon, Se Jin;Ko, Kwang Ho
通讯作者：
Ko, Kwang Ho