Interleukin-1 Beta Exacerbates The Catabolic Effects Of Human Nucleus Pulposus Cells Through Activation Of The Nuclear Factor Kappa B Signaling Pathway Under Hypoxic Conditions

OBJECTIVE: To determine the regulatory role of interleukin 1 beta (IL-1 beta) in the Nuclear Factor kappa B (NF-kappa B) -mediated catabolic effects of the nucleus pulposus cells in human intervertebral disc degeneration under hypoxic conditions.PATIENTS AND METHODS: Human nucleus pulposus cells were cultured and exposed to IL-1 beta under hypoxic or normoxic environments, with or without NF-kappa B inhibition. The cell growth was determined using cell counting kit-8; gene and protein expressions were analyzed by Real-time polymerase chain reaction and Western blotting, respectively.RESULTS: Co-treatment with IL-1 beta and hypoxia decreased cell viability in human nucleus pulposus cells. There was a positive effect of IL-1 beta on human nucleus pulposus cells under hypoxia, which was through the up-regulation of matrix metalloproteinase-3 (MMP-3), MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5. IL-1 beta-induced expressions of MMP-3, MMP-9, ADAMTS-4, and ADAMTS-5 under hypoxia were accompanied by increased activation of NF-kappa B. Inhibition of NF-kappa Bp65 by small interfering RNA or specific inhibitor BAY11-7082 blocked IL-1 beta-dependent gene upregulation of MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 in a hypoxic environment. The gene expression of aggrecan was decreased by IL-1 beta under hypoxic conditions, which was reversed by either BAY11-7082 or NF-kappa Bp65 knockdown.CONCLUSIONS: IL-1 beta and hypoxia synergetically contributed to the catabolic effects of the nucleus pulposus cells by upregulating the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 through the activation of NF-kappa B signaling pathway, indicating that the NF-kappa B signaling pathway is a key mediator of intervertebral disc degeneration.