SIRT1 alleviates IL-1β induced nucleus pulposus cells pyroptosis via mitophagy in intervertebral disc degeneration

International Immunopharmacology(2022)

Cited 16|Views18
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Abstract
•This study is the first time to analyze the potential mechanism of SIRT1 in NLRP3-activated pyroptosis in NPCs.•We found that IL-1β could promote its own production by enhancing NLRP3 inflammasome activation, resulting in an activation positive feedback loop in IL-1β treated NPCs.•We firstly found that SIRT1 overexpression could ameliorate IL-1β induced mitochondrial dysfunction and ROS accumulation, inhibit NLRP3 inflammasome activation by promoting PINK1/Parkin mediated mitophagy.•In the rat model, we firstly confirmed that SIRT1 agonist (SRT1720) treatment decreased the expression of NLRP3, p20, and IL-1β, increased the expression of PINK1 and LC3, delayed IVDD process.\•Taken together, our results indicate that SIRT1 alleviates IL-1β induced NLRP3 inflammasome activation via mitophagy in NPCs, SIRT1 may be a potential therapeutic target to alleviate NLRP3- activated pyroptosis in the inflammatory stress related IVDD.
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Key words
SIRT1,NLRP3 inflammasome,Pyroptosis,Mitophagy,IVDD
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