OBJECTIVE: Previous studies have shown that Quinazoline (QNZ) plays extremely important roles in the cellular physiological activity, but it has been rarely examined on cell behavior following intervertebral disc degeneration (IVDD). The aim of this study was to investigate whether QNZ mediates oxidative stress and inflammation contributed to IL-1β-induced nucleus pulposus (NP) cells degeneration in vitro.
PATIENTS AND METHODS: NP were isolated cells from human disc samples collected from patients and the IL-1β-induced NP cells degenerated model was constructed. The cells were randomly divided into 3 groups, namely, Control group, IL-1β group (10 µM), QNZ + IL-1β group (containing 10 nM QNZ and 10 µM IL-1β). Then, the cell viability was determined by CCK-8 assay, and the levels of collagen I, collagen II, aggrecan, p16, p53, β-galactosidase (β-gal), antioxidant enzymes, 8-hydroxy-2-deoxyguanosine (8-OHdG), NF-κB/MAPKs signaling-related proteins and inflammatory factors were examined using Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in NP cells. Finally, the expressions of IL-1β, IL-6, and TNF-α in the cell supernatants were also determined by enzyme-linked immunosorbent assay (ELISA).
RESULTS: This study showed that IL-1β promoted the progress of IDD, with markedly increased expressions of collagen I, p16, p53, and β-gal, as well as decreased expressions of collagen II and aggrecan. However, QNZ treatment could reverse the effects of IL-1β. It was found that cell proliferation was increased, ROS level was decreased, antioxidant enzymes were upregulated, and inflammatory factors were reduced after QNZ stimulation. Moreover, NF-κB/MAPKs signaling proteins IKKβ, IκBα, p65, ERK, JNK, and p38 were significantly dephosphorylated by QNZ.
CONCLUSIONS: These results indicated that QNZ prevented NP degradation via restraining oxidative stress and inflammation through inhibition of the NF-κB/MAPKs signaling pathway. QNZ may become a novel insight into the therapy of IVDD in the future.Free PDF Download
To cite this article
Z.-B. Chen, Y.-B. Yu, Q.-B. Wa, J.-W. Zhou, M. He, Y. Cen
The role of quinazoline in ameliorating intervertebral disc degeneration by inhibiting oxidative stress and anti-inflammation via NF-κB/MAPKs signaling pathway
Eur Rev Med Pharmacol Sci
Vol. 24 - N. 4