- 作者: Fan-Wei Tseng, Dann-Ying Liou, May-Jywan Tsai, Wen-Cheng Huang , Henrich Cheng
- 作者服務機構: Department and Institute of Pharmacology, School of Medicine, National Yang- Ming University, Taipei, Taiwan R.O.C
- 中文摘要: --
- 英文摘要:
Background:
Acute spinal cord injury (SCI) leads to a series of reactive changes and causes severe neurological deficits. A pronounced inflammation contributes to secondary pathology after SCI. Astroglia respond to SCI by proliferating, migrating, and altering phenotype. The impact of reactive gliosis on the pathogenesis of SCI is not fully understood. Our previous study has identified an inflammatory modulating protein, proliferation related acidic leucine-rich protein (PAL31) which is upregulated in the microglia/macrophage of injured cords. Because PAL31 participates in cell cycle progression and reactive astroglia often appears in the injured cord, we aim to examine whether PAL31 is involved in glial modulation after injury.
Results:
Enhanced PAL31 expression was shown not only in microglia/macrophages but also in spinal astroglia after SCI. Cell culture study reveal that overexpression of PAL31 in mixed glial cells or in C6 astroglia significantly reduced LPS/IFNgamma stimulation. Further, enhanced PAL31 expression in C6 astroglia protected cells from H2O2 toxicity; however, this did not affect its proliferative activity. The inhibiting effect of PAL31 on LPS/IFNgamma stimulation was observed in glia or C6 after co-culture with neuronal cells. The results demonstrated that the overexpressed PAL31 in glial cells protected neuronal damages through inhibiting NF-kB signaling and iNOS.
Conclusions:
Our data suggest that PAL31upregulation might be beneficial after spinal cord injury. Reactive gliosis might become a good target for future therapeutic interventions. - 中文關鍵字: --
- 英文關鍵字: Spinal cord injury, Proliferation related acidic leucine-rich protein, Inflammation, H2O2 toxicity, Astroglia, C6 glioma, Microglia