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

TL;DR: The 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) and suggested that inhibiting NF-kkB pathway can promote autophagy and decrease apoptotic and inflammation response in L PS-induced NPCs.

Abstract: 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.