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

International Immunopharmacology
Yi SunHaining Zhang

Abstract

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 P...Continue Reading

Citations

Sep 20, 2020·Journal of Orthopaedic Surgery and Research·Hong YiWei Liu
Feb 13, 2021·BioMed Research International·Daxue ZhuXuewen Kang
Nov 4, 2020·The Journal of the Acoustical Society of America·Ya-Cherng ChuJaw-Lin Wang
Feb 21, 2021·Osteoarthritis and Cartilage·G Chao-YangZ Hai-Hong
Aug 6, 2021·Journal of Inflammation Research·Shafiu A Umar ShingeFengxu Yu

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