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-1b in 45 degenerate and seven nondegenerate IVD samples. The correlation between the degeneration scores and expression levels of NLRP3, caspase-1, and IL-1b were also analyzed. The mRNA expression levels of the three molecules (NLRP3, caspase-1, and IL-1b) 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-1b. The findings suggest that excessive activation of the NLRP3 inflammasome results in overproduction of downstream IL-1b, 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. Anat Rec,

The NLRP3/Caspase-1/Interleukin-1β Axis Is Active in Human Lumbar Cartilaginous Endplate Degeneration

“…Others have reported that the degenerative changes of the cartilaginous endplate can result in decreasing nutrient supply, low oxygen tension, and accumulated lactic acid, which accelerate the degeneration process [5,15,45]. Furthermore, cartilaginous endplate degeneration of the internal generation of inflammatory substances can lead to local inflammation through the endplate diffusion and then upregulate inflammatory cytokines and thereby accelerate the pathophysiology of nucleus pulposus degeneration [8,32]. Modic changes are MRI signal changes in the vertebral body adjacent to the endplate, which are correlated with degeneration in the extracellular matrix [6].…”

LINC00969 promotes the degeneration of intervertebral disk by sponging miR‐335‐3p and regulating NLRP3 inflammasome activation

“…NOD‐like receptor protein 3 (NLRP3) inflammasomes are essential components of innate immune defense against type 2 diabetes, Alzheimer's disease, and atherosclerosis . Several lines of evidence suggested that excessive activation of the NLRP3 inflammasomes results in the production of downstream caspase‐1 and interleukin (IL)‐1β, which participate in the pathogenesis of IDD and were positively associated with the grades of disk degeneration . Further studies indicated that the activation of thioredoxin‐interacting protein (TXNIP)‐NLRP3 inflammasome signal pathway is closely related to the occurrence and development of IDD .…”

Acidification changes affect the inflammasome in human nucleus pulposus cells

“…The inflammasome has been previously shown to play a role in infections [18–20], metabolic syndromes [21, 22], autoimmune diseases [23–25] and injury [11, 13, 26–28]. A positive correlation between the degree of IDD and inflammasome content in the disc has also been previously reported [29]. …”

“…Accordingly, higher levels of NLRP3 inflammasome proteins correlate with advanced grades of degenerated discs in humans [29]. We have previously shown that the NLRP1 inflammasome is active in neurons of the spinal cord after injury [13].…”