Cystatin F involvement in adenosine A(2A) receptor-mediated neuroinflammation in BV2 microglial cells.
Cystatin F involvement in adenosine A(2A) receptor-mediated neuroinflammation in BV2 microglial cells.
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胱抑素 F 参与 BV2 小胶质细胞腺苷 A2A 受体介导的神经炎症
DOI：
10.1038/s41598-018-25031-5
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发表时间：
2018-05-01
影响因子：
4.6
通讯作者：
Ran H
中科院分区：
文献类型：
--
作者：
Duan W;Wang H;Fan Q;Chen L;Huang H;Ran H
我们之前的研究表明，腺苷A2A R激活可显著促进胱抑素F （cystatin F， CF）的表达，并加重缺氧脑损伤引起的白质病变。因此，我们假设CF可能参与了A2A R激活引起的活化小胶质细胞的神经炎症。我们用CF shRNA载体转染了BV2细胞，并在A2A R被激活或失活的缺氧BV2细胞中检测了促炎细胞因子的产生，以证实这一假设。此外，我们还研究了缺氧激活BV2细胞中A2A R激活对CF表达的可能信号通路。A2A R的激活促进了CF的表达，在BV2细胞低糖和缺氧处理后，CF的表达显著增加。CF基因敲低可显著抑制缺氧- bv2细胞中A2A R活化诱导的促炎细胞因子的表达增加。此外，PKA抑制剂H-89和PKC抑制剂staurosporine可显著抑制缺氧bv2细胞中A2A R活化引起的CF表达增加。因此，这些结果表明缺氧BV2细胞高表达CF， CF通过PKA/CREB和PKC/CREB或ERK1/2信号通路参与A2A R激活介导的神经炎症。
Our previous studies have shown adenosine A2A R activation markedly promotes the expression of cystatin F (CF) and exacerbates the white matter lesions induced by hypoxic brain injuries. Thus, we hypothesized that CF was probably involved in neuroinflammation of activated microglia induced by A2A R activation. We transfected the BV2 cells with a CF shRNA vector and examined the production of pro-inflammatory cytokines in hypoxic-BV2 cells in which A2A R was activated or inactivated to confirm this hypothesis. Additionally, we also investigated the probable signaling pathways involved in modulation of A2A R activation on CF expression in hypoxia-activated BV2 cells. Activation of A2A R promoted CF expression, which was significantly increased after the low glucose and hypoxia treatments in BV2 cells. CF gene knockdown markedly inhibited the increase in the expression of pro-inflammatory cytokines induced by A2A R activation in hypoxic-BV2 cells. Furthermore, the increased expression of the CF induced by A2A R activation was remarkably inhibited in hypoxic-BV2 cells administrated with the PKA inhibitor H-89 and the PKC inhibitor staurosporine. Hence, these results indicate that hypoxia BV2 cells highly express CF, which is involved in A2A R activation-mediated neuroinflammation via the PKA/CREB and PKC/CREB or ERK1/2 signaling pathways.
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影响因子：
5.4
作者：
Langerholc, T;Zavasnik-Bergant, V;Kos, J
通讯作者：
Kos, J
DOI：
10.1074/jbc.m111.253914
发表时间：
2011-12-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Colbert JD;Matthews SP;Kos J;Watts C
通讯作者：
Watts C
影响因子：
6.4
作者：
Izzotti, Alberto;Pulliero, Alessandra;Fazzi, Elisa
通讯作者：
Fazzi, Elisa
腺苷A2A受体缺乏症上调囊蛋白F表达在由慢性脑部灌注诱导的白质病变中。
影响因子：
3.7
作者：
Duan W;Ran H;Zhou Z;He Q;Zheng J
通讯作者：
Zheng J
影响因子：
4.4
作者：
Duan, Wei;Gui, Li;Zheng, Jian
通讯作者：
Zheng, Jian