IL-17A Inhibits Autophagy By Activating The PI3K/Akt/Bcl-2 Signaling Pathway In Degenerated Human Nucleus Pulposus Cells

Objective: Interverterabl disc degeneration(IDD)is a complicated process which is regulated by multiple factors.Autophagy is thought to be protective mechanism in occurrence and development of IDD.IL-17 are a group of inflammation factors that are associated with autoimmune diseases and play an important role in process of IDD including inflammation response,degradation of extracellular matrix(ECM),production of cytokines.This research is to explore IL-17 A can suppress the autophagy in degenerated human nucleus pulposus cells through activating of PI3K/Akt/Bcl-2 signaling pathwayMethods:Collect the specimens from patients with IDD to conduct the isolation and cultivation of degenerated nucleus pulposus(NP)cells.IL-17 A was used to treat NP cells.Western Blot and Monodansylcadaverine(MDC)were used to detected the the effects of IL-17 A in expression of autophagy-related protein p62 and LC3 and autophagosome.LY249002(PI3Kinhibitor),Perifosine(Akt inhibitor),ABT-737(Bcl-2 inhibitor)were used and the protein expression level of downstream regulator factors were detected by Western BlotResults:Western Blot reveal that IL-17 A can suppress the autophagy level in human degenerated NP cells and exhibit time-dependent and dose-dependent manner.Result of MDC showed that IL-17 A can significantly inhibit the formation of autophagosome.Western Blot revealed that IL-17 A can upregulate the protein expression of PI3 K,Akt and Bcl-2.Moreover,the inhibit effect of IL-17 in NP cell autophagy can be reverse by the LY249002,Perifosine,ABT-737(p<0.05).When LY294002 was used,the downstream element Akt and Bcl-2 was inhibited as well but not in IL-17 A group.When perifosine was added,the Bcl-2 was inhibited but not in IL-17 A group.When ABT-737 was used,the Beclin-1 protein was detected to imcreaseSummary:1.IL-17 A can suppress the autopohagy level in human degenerated NP cells and this effect exhibit time-dependent and dose-dependent manner;2.IL-17 A can inhibit autophagy in NP cells by activating PI3K/Akt/Bcl-2 signaling pathway.Conclusion:In human degenerated NP cells,IL-17 A can suppress autophagy through activating PI3K/Akt/Bcl-2 signaling pathway.