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.