Exp Cell Res.2020 Dec 9;398(2):112418. doi: 10.1016/j.yexcr.2020.112418

NIMA-related kinase 7 amplifies NLRP3 inflammasome pro-inflammatory signaling in microglia/macrophages and mice models of spinal cord injury

Xubiao Ji  1 Zhiwen Song  2 Junsheng He  2 Shiwu Guo  2 Yuwei Chen  2 Honghai Wang  2 Jinlong Zhang  2 Xu Xu  2 Jinbo Liu  3

  • 1 Department of Spinal Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China; Department of Orthopedics, The Affiliated Wujin Hospital of Jiangsu University, Changzhou, 213003, China.
  • 2 Department of Spinal Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
  • 3 Department of Spinal Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China. Electronic address: czljbljb@126.com.

Abstract

Background: NIMA-related kinase-7 (NEK7) is a serine/threonine kinase that drives cell-cycle dynamics by modulating mitotic spindle formation and cytokinesis. It is also a crucial modulator of the pro-inflammatory effects of NOD-like receptor 3 (NLRP3) inflammasome. However, the role of NEK7 in microglia/macrophages post-spinal cord injury (SCI) is not well defined.

Methods: In this study, we performed both in vivo and in vitro experiments. Using an in vivo mouse SCI model, NEK7 siRNAs were administered intraspinally. For in vitro analysis, BV-2 microglia cells with NEK7-siRNA were stimulated with 1 μg/ml lipopolysaccharide (LPS) and 2 mM Adenosine triphosphate (ATP).

Results: Here, we found that the mRNA and protein levels of NEK7 and NLRP3 inflammasomes were upregulated in spinal cord tissues of injured mice and BV-2 microglia cells exposed to Lipopolysaccharide (LPS) and Adenosine triphosphate (ATP). Further experiments established that NEK7 and NLRP3 interacted in BV-2 microglia cells, an effect that was eliminated following NEK7 ablation. Moreover, NEK7 ablation suppressed the activation of NLRP3 inflammasomes. Although NEK7 inhibition did not significantly improve motor function post-SCI in mice, it was found to attenuate local inflammatory response and inhibit the activation of NLRP3 inflammasome in microglia/macrophages of the injured spinal cord.

Conclusion: NEK7 amplifies NLRP3 inflammasome pro-inflammatory signaling in BV-2 microglia cells and mice models of SCI. Therefore, agents targeting the NEK7/NLRP3 signaling offers great promise in the treatment of inflammatory response post-SCI.

Keywords: Inflammasome; Microglia/Macrophage; NEK7; NLRP3; Spinal cord injury.

在线客服
在线客服
热线电话
关注微信/技术支持
0