title: Enhanced NLRP3, caspase-1, and IL- 1β levels in degenerate human intervertebral disc and their association with the grades of disc degeneration.
abstract: The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome plays an important role in a variety of diseases. However, the role of NLRP3 in the human intervertebral disc (IVD) degeneration remains unknown. In the present study, we assessed the expression levels of the NLRP3 inflammasome and its downstream targets caspase-1 and IL-1β in 45 degenerate and seven nondegenerate IVD samples. The correlation between the degeneration scores and expression levels of NLRP3, caspase-1, and IL-1β were also analyzed. The mRNA expression levels of the three molecules (NLRP3, caspase-1, and IL-1β) were higher in the degenerate IVDs group than the controls (nondegenerate IVDs group). Immunohistochemistry showed that the expression levels of all three molecules were markedly increased in the nucleus pulposus of degenerate IVDs compared with nondegenerate IVDs. There was a positive correlation between the degeneration scores and the expression levels of the NLRP3 inflammasome as well as its downstream targets caspase-1 and IL-1β. The findings suggest that excessive activation of the NLRP3 inflammasome results in overproduction of downstream IL-1β, which participates in the pathogenesis of human IVD degeneration. Therefore, the NLRP3 inflammasome might serve as a potential therapeutic target for the prevention and treatment of IVD degeneration.
authors.affiliation: Department of Anesthesiology, Shaoxing People's Hospital and Shaoxing Hospital of Zhejiang University, Shaoxing, People's Republic of China.
authors.forename: Zhong-Hua
authors.initials: ZH
authors.lastname: Chen
authors.forename: Shen-Hui
authors.initials: SH
authors.lastname: Jin
authors.forename: Min-Yan
authors.initials: MY
authors.lastname: Wang
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Jin
authors.forename: Chen
authors.initials: C
authors.lastname: Lv
authors.forename: Ying-Feng
authors.initials: YF
authors.lastname: Deng
authors.forename: Jun-Lu
authors.initials: JL
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D055959:Intervertebral Disc Degeneration / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017116:Low Back Pain / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008159:Lumbar Vertebrae / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012720:Severity of Illness Index; D013123:Spinal Fusion; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D020170:Caspase 1
keywords: NLRP3 inflammasome; caspase-1; human intervertebral disc degeneration; interleukin-1β