PMID- 30468453
OWN - NLM
STAT- MEDLINE
DCOM- 20191119
LR  - 20191119
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 22
IP  - 21
DP  - 2018 Nov
TI  - Interleukin-1beta exacerbates the catabolic effects of human nucleus pulposus cells 
      through activation of the Nuclear Factor kappa B signaling pathway under hypoxic 
      conditions.
PG  - 7129-7139
LID - 16244 [pii]
LID - 10.26355/eurrev_201811_16244 [doi]
AB  - OBJECTIVE: To determine the regulatory role of interleukin 1 beta (IL-1beta) in the 
      Nuclear Factor kappa B (NF-kappaB) -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-1beta under hypoxic or normoxic environments, with or without NF-kappaB 
      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-1beta and hypoxia 
      decreased cell viability in human nucleus pulposus cells. There was a positive 
      effect of IL-1beta 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-1beta-induced expressions of MMP-3, MMP-9, ADAMTS-4, and ADAMTS-5 under hypoxia 
      were accompanied by increased activation of NF-kappaB. Inhibition of NF-kappaBp65 by 
      small interfering RNA or specific inhibitor BAY11-7082 blocked IL-1beta-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-1beta under hypoxic 
      conditions, which was reversed by either BAY11-7082 or NF-kappaBp65 knockdown. 
      CONCLUSIONS: IL-1beta 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-kappaB signaling pathway, 
      indicating that the NF-kappaB signaling pathway is a key mediator of intervertebral 
      disc degeneration.
FAU - Sun, Z-Y
AU  - Sun ZY
AD  - Shanghai Songjiang District Central Hospital, Shanghai, China. tjw609@163.com.
FAU - Liu, Y-T
AU  - Liu YT
FAU - Liang, H
AU  - Liang H
FAU - Li, Y
AU  - Li Y
FAU - Wang, D-G
AU  - Wang DG
FAU - Tian, J-W
AU  - Tian JW
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Aggrecans)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Adult
MH  - Aggrecans/genetics
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Humans
MH  - Hypoxia/metabolism
MH  - Interleukin-1beta/*metabolism
MH  - Intervertebral Disc Degeneration/metabolism/*pathology
MH  - Middle Aged
MH  - NF-kappa B/*metabolism
MH  - Nucleus Pulposus/*cytology
MH  - Signal Transduction/drug effects
MH  - Young Adult
EDAT- 2018/11/24 06:00
MHDA- 2019/11/20 06:00
CRDT- 2018/11/24 06:00
PHST- 2018/11/24 06:00 [entrez]
PHST- 2018/11/24 06:00 [pubmed]
PHST- 2019/11/20 06:00 [medline]
AID - 16244 [pii]
AID - 10.26355/eurrev_201811_16244 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2018 Nov;22(21):7129-7139. doi: 
      10.26355/eurrev_201811_16244.