Impact of NF-κB pathway on the apoptosis-inflammation-autophagy crosstalk in human degenerative nucleus pulposus cells

The NF-κB pathway has been reported to play a very important role in the process of intervertebral disc degeneration (IVDD). Our results demonstrated that knockdown of NF-κB with P65-siRNA can significantly decrease cell Apoptosis and the expression of pro-inflammation factors TNF-α and IL-1β in LPS-induced nucleus pulposus cells (NPCs). However, the molecular mechanism of NF-κB pathway exerting anti-inflammation and anti-apoptosis function remains unclear. Some researchers reported that inhibiting NF-κB pathway can attenuate the catabolic effect by promoting Autophagy during inflammatory conditions in rat nucleus pulposus cells. Therefore, we hypothesized that in human NPCs, inhibiting NF-κB pathway may also promote Autophagy. Our results indicated that after knockdown of NF-κB, the Autophagy was significantly increased and the expression of p-AKT and p-mTOR protein markedly decreased, but the level of Autophagy was inhibited after treatment with Akt Activator SC79, suggesting the involvement of Akt/mTOR-mediated Autophagy was under Autophagy activation. However, both LPS-induced NPCs Apoptosis and expression of pro-inflammation factors were further increased by pretreatment with the Autophagy Inhibitor chloroquine (CQ). These suggested that inhibiting NF-κB pathway can promote Autophagy and decrease Apoptosis and inflammation response in LPS-induced NPCs. Meanwhile, Autophagy triggered by NF-κB inhibition plays a protective role against Apoptosis and inflammation.