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Interleukin-1β exacerbates the catabolic effects of human nucleus pulposus cells through activation of the Nuclear Factor kappa B signaling pathway under hypoxic conditions.
Eur Rev Med Pharmacol Sci. 2018 11; 22(21):7129-7139.ER

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 with 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.

Authors+Show Affiliations

Shanghai Songjiang District Central Hospital, Shanghai, China. tjw609@163.com.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30468453

Citation

Sun, Z-Y, et al. "Interleukin-1β Exacerbates the Catabolic Effects of Human Nucleus Pulposus Cells Through Activation of the Nuclear Factor Kappa B Signaling Pathway Under Hypoxic Conditions." European Review for Medical and Pharmacological Sciences, vol. 22, no. 21, 2018, pp. 7129-7139.
Sun ZY, Liu YT, Liang H, et al. Interleukin-1β exacerbates the catabolic effects of human nucleus pulposus cells through activation of the Nuclear Factor kappa B signaling pathway under hypoxic conditions. Eur Rev Med Pharmacol Sci. 2018;22(21):7129-7139.
Sun, Z. Y., Liu, Y. T., Liang, H., Li, Y., Wang, D. G., & Tian, J. W. (2018). Interleukin-1β exacerbates the catabolic effects of human nucleus pulposus cells through activation of the Nuclear Factor kappa B signaling pathway under hypoxic conditions. European Review for Medical and Pharmacological Sciences, 22(21), 7129-7139. https://doi.org/10.26355/eurrev_201811_16244
Sun ZY, et al. Interleukin-1β Exacerbates the Catabolic Effects of Human Nucleus Pulposus Cells Through Activation of the Nuclear Factor Kappa B Signaling Pathway Under Hypoxic Conditions. Eur Rev Med Pharmacol Sci. 2018;22(21):7129-7139. PubMed PMID: 30468453.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-1β exacerbates the catabolic effects of human nucleus pulposus cells through activation of the Nuclear Factor kappa B signaling pathway under hypoxic conditions. AU - Sun,Z-Y, AU - Liu,Y-T, AU - Liang,H, AU - Li,Y, AU - Wang,D-G, AU - Tian,J-W, PY - 2018/11/24/entrez PY - 2018/11/24/pubmed PY - 2019/11/20/medline SP - 7129 EP - 7139 JF - European review for medical and pharmacological sciences JO - Eur Rev Med Pharmacol Sci VL - 22 IS - 21 N2 - 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 with 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. SN - 2284-0729 UR - https://www.unboundmedicine.com/medline/citation/30468453/Interleukin_1β_exacerbates_the_catabolic_effects_of_human_nucleus_pulposus_cells_through_activation_of_the_Nuclear_Factor_kappa_B_signaling_pathway_under_hypoxic_conditions_ L2 - https://www.europeanreview.org/article/16244 DB - PRIME DP - Unbound Medicine ER -