Piezo1 activates the NLRP3 inflammasome in nucleus pulposus cell-mediated by Ca2+/NF-κB pathway

• Published in: International immunopharmacology Vol. 85; p. 106681
• Main Authors: Sun, Yi, Leng, Ping, Song, Mengxiong, Li, Dawei, Guo, Pengcheng, Xu, Xipeng, Gao, Huanshen, Li, Zhenghui, Li, Chenkai, Zhang, Haining
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.2020; Elsevier BV
• Subjects: Assembly; Calcium; Calcium ions; Caspase-1; Cell activation; Degeneration; Degenerative disc disease; IL-1β; Inflammasomes; Inflammation; Interleukins; Intervertebral disc degeneration; Intervertebral discs; Ion channels; NF-κB protein; NLR family; Nuclei (cytology); Nucleus pulposus; Pathogenesis; Piezo1 ion channel; Priming; siRNA; Time dependence; Transfection; Intervertebral disc degeneration; NLR family; Piezo1 ion channel
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106681

The activation of Piezo1 in nucleus pulposus cells exposed to mechanical stretch resulted in an increase in intracellular calcium load. On the one hand, the increased calcium concentration promoted the expression of NLRP3 and proIL-1β by activating NF-κB pathway while on the other hand; it acted as second signal to promote assembly of NLRP3 inflammasome which increased the secretion of IL-1β. [Display omitted] •Mechanical stretch promote activation of NLRP3 inflammasome in nucleus pulposus cells.•Silence of Piezo1 decrease inflammation of nucleus pulposus cells caused by mechanical stretch.•Ca2+/NF-κB pathway is involved in the priming and assembly of NLRP3 inflammasome. Studying and understanding the mechanism of inflammation in nucleus pulposus is the key to understand and prevent intervertebral disc degeneration. We propose a model of mechanical sensitive ion channel Piezo1 mediated inflammation of nucleus pulposus cells. Piezo1 can up-regulate the level of interleukin-1β (IL-1β) in nucleus pulposus cells once it is activated. It is suggested that Piezo1 may mediate inflammation by activating Nod-like receptor protein 3 (NLRP3) inflammasome to accelerate the production and maturation of IL-1β. The primary objective of this study was to explore whether Piezo1 activates NLRP3 inflammasome in nucleus pulposus cells. Piezo1 sensitization was induced by mechanical stretch following which we analyzed the priming and assembly of NLRP3 inflammasome and also studied if the downstream Ca2+/NF-κB pathway mediated this activation in nucleus pulposus cells. The expression of Piezo1 and NLRP3 inflammasome increased in a time-dependent manner upon mechanical stretch. Piezo1 activation promoted NLRP3 inflammasome assembly, which was demonstrated by the upregulation of caspase-1 activation and IL-1β production. Transfection of Piezo1-siRNA reversed this process. The inhibition of Ca2+/NF-κB pathway reduced Piezo1-dependent activation of NLRP3 inflammasome. Thus, we propose that activation of NLRP3 inflammasome in nucleus pulposus cells mediated by Piezo1 through the Ca2+/NF-κB pathway is a novel pathogenesis for the progress of intervertebral disc degeneration. As per our knowledge this is the first study which has provided evidence linking Piezo1-mediated inflammation in nucleus pulposus cells with the production of NLRP3 inflammasome.