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- Title
Interleukin-1β exacerbates the catabolic effects of human nucleus pulposus cells through activation of the Nuclear Factor kappa B signaling pathway under hypoxic conditions.
- Authors
SUN, Z.-Y.; LIU, Y.-T.; LIANG, H.; LI, Y.; WANG, D.-G.; TIAN, J.-W.
- Abstract
OBJECTIVE: To determine the regulatory role of interleukin 1 beta (IL-1β) in the Nuclear Factor kappa B (NF-κB) -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-1β under hypoxic or normoxic environments, with or without NF-κB 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 w ith IL-1β and hypoxia decreased cell viability in human nucleus pulposus cells. There was a positive effect of IL-1β 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-1β-induced expressions of MMP-3, MMP-9, ADAMTS-4, and ADAMTS-5 under hypoxia were accompanied by increased activation of NF-κB. Inhibition of NF- κBp65 by small interfering RNA or specific inhibitor BAY11-7082 blocked IL-1β-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-1β under hypoxic conditions, which was reversed by either BAY11-7082 or NF-κBp65 knockdown. CONCLUSIONS: IL-1β 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-κB signaling pathway, indicating that the NF-κB signaling pathway is a key mediator of intervertebral disc degeneration.
- Subjects
NF-kappa B; INTERLEUKIN-1; CELL growth; PROTEIN expression; HYPOXEMIA
- Publication
European Review for Medical & Pharmacological Sciences, 2018, Vol 22, Issue 21, p7129
- ISSN
1128-3602
- Publication type
Article