Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation in vivo and in vitro After Infrasound Exposure

• Main Authors: Ya-Jun Shi, Ming Shi, Li-Jun Xiao, Li Li, Lin-Hui Zou, Chao-Yang Li, Qin-Jun Zhang, Lin-Fu Zhou, Xin-Chao Ji, Huan Huang, Ye Xi, Ling Liu, Hong-Ya Zhang, Gang Zhao, Lei Ma
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-08-01
• Series: Frontiers in Neuroscience
• Subjects: infrasound; hippocampus; astrocytes; FGF2; FGFR1; NF-κB
• Online Access: https://www.frontiersin.org/article/10.3389/fnins.2018.00582/full

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 in vivo and in vitro. 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 in vitro and in vivo. 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 in vitro and in vivo. Taken together, our findings showed that FGF2/FGFR1 pathway may exert inhibitive effects on astrocyte-mediated neuroinflammation in vitro and in vivo after infrasound exposure.