Zhao An-Peng, Dong Yin-Feng, Liu Wei, Gu Jun, Sun Xiu-Lan
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, China.
CNS Neurosci Ther. 2014 Feb;20(2):147-53. doi: 10.1111/cns.12178. Epub 2013 Nov 20.
Our previous studies have demonstrated adenosine triphosphate-sensitive potassium channel (KATP channel) openers could protect against inflammatory response in brain disease, but little is known about the mechanisms involved in KATP channel openers inhibiting neuroinflammation.
In the present study, we found that oxygen-glucose deprivation (OGD) resulted in BV-2 cells activation, significantly increased tumor necrosis factor-alpha and interleukin-1beta (IL-1β) levels, accompanied by downregulating Kir6.1 subunit. Pretreatment with nicorandil, a KATP channel opener, could attenuate OGD-induced BV-2 cells activation and inhibit pro-inflammatory factors release. Further study demonstrated that OGD activated Toll-like receptor-4 (TLR4) signaling pathway and NOD-like receptor pyrin domain containing three inflammasome, thereby increased IL-1β production. Pretreatment with nicorandil could reverse the two pathways involved in IL-1β production.
Our findings reveal that KATP channel openers could protect against OGD-induced neuroinflammation via inhibiting inflammasome activation and TLR4 signal transduction.
我们之前的研究表明，三磷酸腺苷敏感性钾通道（KATP通道）开放剂可在脑部疾病中对抗炎症反应，但关于KATP通道开放剂抑制神经炎症的机制知之甚少。
在本研究中，我们发现氧糖剥夺（OGD）导致BV-2细胞活化，显著增加肿瘤坏死因子-α和白细胞介素-1β（IL-1β）水平，同时伴随着Kir6.1亚基下调。用KATP通道开放剂尼可地尔预处理可减轻OGD诱导的BV-2细胞活化，并抑制促炎因子释放。进一步研究表明，OGD激活了Toll样受体4（TLR4）信号通路和含NOD样受体吡咯结构域蛋白3炎性小体，从而增加IL-1β的产生。尼可地尔预处理可逆转参与IL-1β产生的这两条途径。
我们的研究结果表明，KATP通道开放剂可通过抑制炎性小体活化和TLR4信号转导来对抗OGD诱导的神经炎症。
