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

Abstract

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.

FGF/FGFR signaling in health and disease

“… 523 However, FGF2/FGFR1 pathway has inhibitive effects on astrocyte-mediated neuroinflammation after infrasound exposure. 524 In turn, there is a profound reduction in FGFR1 in human umbilical vein ECs treated by TNF-α and IL-1β, while other inflammatory cytokines such as IL-6 could not inhibit the expression of FGFR1. 476 Besides, our group recently identified that FGFR3 deficiency promoted chemotaxis of macrophages via activation of NF-κB/CXCR7 signaling pathway, which reveals the negative role of FGFR3 in synovial inflammatory response.…”

Effects of FGF2/FGFR1 Pathway on Expression of A1 Astrocytes After Infrasound Exposure

“…Furthermore, human and animal experiments have suggested that prolonged infrasound exposure can damage the central nervous system (CNS), including the hippocampus, cerebellum, limbic-corticular complex, hypothalamus, and cortex (Izmerov et al, 1997; Fei et al, 2000; Yuan et al, 2009; Shi et al, 2013; Cai et al, 2014; Ma et al, 2015). We previously confirmed that infrasound exposure activated astrocytes and induced neuronal apoptosis in the CNS, which subsequently impaired spatial learning and memory abilities (Shi et al, 2013, 2018).…”

“…The rats were divided randomly into groups as described previously (Shi et al, 2018): control group (no infrasound exposure, n = 6), infrasound (IS) exposure groups (exposed to 16 Hz, 150 dB of infrasound for 1, 3, 5, or 7 days, n = 6 per group), FGF2 groups (treated with FGF2 for 1, 3, 5, or 7 days, n = 6 per group), PD groups (treated with PD173074 for 1, 3, 5, or 7 days, n = 6 per group), FGF2+IS groups (infrasound-exposed rats treated with FGF2, n = 6 per group), and PD + IS groups (infrasound-exposed rats treated with PD173074, n = 6 per group). For FGF2 administration, rats were injected intraperitoneally (i.p.)…”

“…We previously showed that the fibroblast growth factor (FGF)2/FGF receptor (FGFR)1 pathway inhibited astrocyte-mediated neuroinflammation in vitro and in vivo after infrasound exposure (Shi et al, 2018), suggesting that the reactivity of A1 astrocytes was related to activation of this pathway. We therefore investigated the role of the FGF2/FGFR1 pathway in infrasound-induced changes of A1 astrocytes in rats pretreated with FGF2 or the selective FGFR1 inhibitor, PD173074 (Mohammadi et al, 1998).…”

Acoustics and Biological Structures

“…Inhibition of the FGF2/FGFR1 pathway aggravated astrocyte-mediated inflammation after infrasonic exposure. The authors concluded that astrocyte-mediated inflammation was involved in infrasound-induced neuronal damage and that the FGF2/FGFR1 pathway played a key role [56].…”