Activating alpha 7 nicotinic acetylcholine receptor inhibits NLRP3 inflammasome through regulation of beta-arrestin-1

文献类型： 外文期刊

第一作者： Ke, Ping

作者： Ke, Ping;Shao, Bo-Zong;Xu, Zhe-Qi;Liu, Chong;Ke, Ping;Chen, Xiong-Wen;Wei, Wei

作者机构：

关键词： alpha 7nAChR;beta-arrestin-1;neuroinflammation;NLRP3 inflammasome

期刊名称：CNS NEUROSCIENCE & THERAPEUTICS （ 影响因子：5.243； 五年影响因子：4.977 ）

ISSN： 1755-5930

年卷期： 2017 年 23 卷 11 期

页码：

收录情况： SCI

摘要： AimsTo evaluate whether activating 7 nicotinic acetylcholine receptor (7nAChR) could inhibit the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome through regulation of -arrestin-1 in monocyte/macrophage system, thus contributing to the control of neuroinflammation. MethodsThe protein levels of NLRP3, caspase-1 (Casp-1) p20 and proCasp-1, interleukin-1 (IL-1) p17 and proIL-1, IL-18 and proIL-18 were measured using Western blotting. The mRNA levels of Casp-1 and IL-1 were detected by real-time PCR (RT-PCR). The colocalization and interaction of NLRP3 protein and -arrestin-1 were measured by immunofluorescence staining and immunoprecipitation. ResultsThe expression of -arrestin-1 was significantly increased and colocalized with CD45-positive cells in spinal cord of experimental auto-immune encephalomyelitis (EAE) mice when compared with the sham mice, which was attenuated by pretreatment with PNU282987, a specific 7nAChR agonist. PNU282987 also significantly inhibited the activation of NLRP3 inflammasome and thus decreased the production of IL-1 and IL-18 both in lipopolysaccharide (LPS)/ATP-stimulated BV2 microglia in vitro and spinal cord from EAE mice in vivo, while inverse effects were observed in 7nAChR knockout mice. Furthermore, overexpression of -arrestin-1 attenuated the inhibitory effect of PNU282987 on NLRP3 inflammasome activation in LPS/ATP-stimulated BV2 microglia. PNU282987 inhibited the interaction between -arrestin-1 and NLRP3 protein in vitro. ConclusionsThe present study demonstrates that activating 7nAChR can lead to NLRP3 inflammasome inhibition via regulation of -arrestin-1 in monocyte/microglia system.

分类号：

  • 相关文献

[1]Activating Cannabinoid Receptor 2 Alleviates Pathogenesis of Experimental Autoimmune Encephalomyelitis Via Activation of Autophagy and Inhibiting NLRP3 Inflammasome. Shao, Bo-Zong,Ke, Ping,Xu, Zhe-Qi,Zhou, Jv-Xiang,Liu, Chong,Wei, Wei. 2014

[2]Autophagy Plays an Important Role in Anti-inflammatory Mechanisms Stimulated by Alpha7 Nicotinic Acetylcholine Receptor. Shao, Bo-Zong,Ke, Ping,Xu, Zhe-Qi,Cheng, Ming-He,Han, Bin-Ze,Su, Ding-Feng,Liu, Chong,Wei, Wei,Chen, Xiong-Wen. 2017

[3]Neuroprotection effect of interleukin ( IL)-17 secreted by reactive astrocytes is emerged from a high-level IL-(17)-containing environment during acute neuroinflammation. Hu, M. H.,Zheng, Q. F.,Jia, X. Z.,Li, Y.,Dong, Y. C.,Wang, C. Y.,Lin, Q. Y.,Zhang, F. Y.,Xu, H. W.,Ren, H.,Hu, M. H.,Zheng, Q. F.,Jia, X. Z.,Li, Y.,Dong, Y. C.,Wang, C. Y.,Lin, Q. Y.,Zhang, F. Y.,Xu, H. W.,Ren, H.,Zhao, R. B.,Zhou, J. H.,Yuan, H. P.,Zhang, W. H.. 2014

作者其他论文 更多>>

微信小程序