Shi Ya-Jun, Shi Ming, Xiao Li-Jun, Li Li, Zou Lin-Hui, Li Chao-Yang, Zhang Qin-Jun, Zhou Lin-Fu, Ji Xin-Chao, Huang Huan, Xi Ye, Liu Ling, Zhang Hong-Ya, Zhao Gang, Ma Lei
Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
31668 Troops of PLA, Army Medical University, Xining, China.
Front Neurosci. 2018 Aug 24;12:582. doi: 10.3389/fnins.2018.00582. eCollection 2018.
Infrasound, a kind of ambient noise, can cause severe disorders to various human organs, specially to central nervous system (CNS). Our previous studies have shown that infrasound-induced CNS injury was closely related with astrocytes activation and astrocytes-mediated neuroinflammation, but the underlying molecular mechanisms are still largely unclear. FGF2/FGFR1 (Fibroblast growth factor 2/Fibroblast growth factor receptor 1) pathway was reported to play an important role in anti-inflammation in CNS disorders. To further study the possible roles of FGF2/FGFR1 pathway in infrasound-induced CNS injury, here we exposed Sprague-Dawley rats or cultured astrocytes to 16 Hz, 150 dB infrasound, and explored the effects of FGF2 on infrasound-induced astrocytes activation and neuroinflammation. Western blotting, immunofluorescence and liquid chip method were used in this experiment. Our results showed that after 3- or 7-day exposure (2 h/day) of rats as well as 2 h exposure of cultured astrocytes to 16 Hz, 150 dB infrasound, astrocyte-expressed FGFR1 was downregulated and . FGF2 pretreatment not only inhibited infrasound-induced astrocyte activation in rat hippocampal CA1 region, but also reduced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-18, IL-6, and IFN-γ and . However, FGF2 significantly upregulated the expression of FGFR1. Furthermore, we showed that FGF2 could attenuate IκBα phosphorylation, NF-κB p65 translocation, pro-inflammatory cytokines levels, and neuronal loss in the CA1 region induced by infrasound. On the contrary, PD173074, a special antagonist of FGFR1, could reverse the effects above and . Taken together, our findings showed that FGF2/FGFR1 pathway may exert inhibitive effects on astrocyte-mediated neuroinflammation and after infrasound exposure.
次声作为一种环境噪声，可对人体多个器官尤其是中枢神经系统（CNS）造成严重损害。我们之前的研究表明，次声诱导的CNS损伤与星形胶质细胞激活及星形胶质细胞介导的神经炎症密切相关，但其潜在分子机制仍不清楚。据报道，成纤维细胞生长因子2/成纤维细胞生长因子受体1（FGF2/FGFR1）通路在中枢神经系统疾病的抗炎过程中发挥重要作用。为进一步研究FGF2/FGFR1通路在次声诱导的CNS损伤中的可能作用，我们将Sprague-Dawley大鼠或培养的星形胶质细胞暴露于16 Hz、150 dB的次声中，探讨FGF2对次声诱导的星形胶质细胞激活和神经炎症的影响。本实验采用蛋白质免疫印迹法、免疫荧光法和液相芯片法。结果显示，大鼠暴露于16 Hz、150 dB次声3天或7天（每天2小时）以及培养的星形胶质细胞暴露2小时后，星形胶质细胞表达的FGFR1下调。FGF2预处理不仅抑制了次声诱导的大鼠海马CA1区星形胶质细胞激活，还降低了肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-18、白细胞介素-6和干扰素-γ等促炎细胞因子的水平。然而，FGF2显著上调了FGFR1的表达。此外，我们发现FGF2可减轻次声诱导的CA1区IκBα磷酸化、NF-κB p65易位、促炎细胞因子水平及神经元丢失。相反，FGFR1特异性拮抗剂PD-173074可逆转上述作用。综上所述，我们的研究结果表明，FGF2/FGFR1通路可能在次声暴露后对星形胶质细胞介导的神经炎症发挥抑制作用。
