NIMA-related kinase 7 amplifies NLRP3 inflammasome pro-inflammatory signaling in microglia/macrophages and mice models of spinal cord injury
| Autor: | Xu Xu, Jinlong Zhang, Zhiwen Song, Junsheng He, Honghai Wang, Xubiao Ji, Yuwei Chen, Jinbo Liu, Shi-Wu Guo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Lipopolysaccharide Inflammasomes Biology Mice 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate 0302 clinical medicine Downregulation and upregulation In vivo NLR Family Pyrin Domain-Containing 3 Protein medicine Animals NIMA-Related Kinases RNA Messenger Receptor Cells Cultured Spinal Cord Injuries integumentary system Microglia Kinase Macrophages Inflammasome Cell Biology Cell biology Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Female Adenosine triphosphate Signal Transduction medicine.drug |
| Zdroj: | Experimental Cell Research. 398:112418 |
| ISSN: | 0014-4827 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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