Interleukin-1β Promotes Schwann Cells De-Differentiation in Wallerian Degeneration via the c-JUN/AP-1 Pathway

Schwann cells (SCs) de-differentiate in Wallerian degeneration (WD) following nerve injury and, by doing so, can actively promote nerve repair and functional recovery. An innate-immune response is an important component of the complex of events referred to as WD. Damaged peripheral nervous system SCs produce IL-1 beta and other inflammatory cytokines. We hypothesized that, in addition to a role in immune responses, IL-1 beta participates in de-differentiation and proliferation of SCs. qPCR and ELISA demonstrated that expression of IL-1 beta mRNAs and protein increased after nerve injury. Immunofluorescent staining and western blotting demonstrated that expression of the p75 neurotrophin receptor (p75NTR) was significantly increased and levels of myelin protein zero (MPZ) were significantly decreased after IL-1 beta exposure compared with control groups in vitro WD. Additionally, qPCR demonstrated that IL-1 beta elevated expression of the de-differentiation gene p75NTR and decreased expression of myelination locus MPZ and promoted SCs de-differentiation. Furthermore, immunofluorescent staining, western blotting, qPCR and ELISA revealed that IL-1 beta promoted c-JUN expression and activation of AP-1 activity of SCs in an in vitro WD model. Finally, Immunofluorescent staining illustrated that IL-1 beta elevated expression of Ki67 in SCs nuclei, the apoptosis of SCs were detected by TUNEL. SCs of WD produce IL-1 beta which promotes SCs de-differentiation and proliferation.