Interleukin-1β Promotes Schwann Cells De-Differentiation in Wallerian Degeneration via the c-JUN/AP-1 Pathway
Interleukin-1β Promotes Schwann Cells De-Differentiation in Wallerian Degeneration via the c-JUN/AP-1 Pathway
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Interleukin-1 beta 通过 c-JUN/AP-1 途径促进华勒变性中雪旺细胞去分化
DOI：
10.3389/fncel.2019.00304
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发表时间：
2019-07-09
影响因子：
5.3
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Chen, Gang;Luo, Xiaohe;Wang, Wei
在神经损伤后的沃勒变性（WD）中，雪旺细胞（SC）去分化，并且通过这样做，可以积极促进神经修复和功能恢复。先天免疫应答是称为WD的事件复合体的重要组成部分。受损的外周神经系统SC产生IL-1 β和其他炎性细胞因子。我们假设，除了在免疫应答中的作用外，IL-1 β还参与了SC的去分化和增殖。qPCR和ELISA结果显示，神经损伤后IL-1 β mRNA和蛋白表达增加。免疫荧光染色和蛋白质印迹显示，与对照组相比，IL-1 β暴露于体外WD后，p75神经营养因子受体（p75 NTR）的表达显著增加，髓鞘蛋白零（MPZ）的水平显著降低。此外，qPCR证实IL-1 β提高去分化基因p75 NTR的表达，降低髓鞘形成位点MPZ的表达，并促进SC去分化。免疫荧光染色、Western blotting、qPCR和ELISA结果显示，IL-1 β可促进WD模型中SC的c-JUN表达和AP-1活性的激活。免疫荧光染色显示IL-1 β可上调SC核内Ki 67的表达，TUNEL法检测SC凋亡。WD的SC产生促进SC去分化和增殖的IL-1 β。
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.