title: Cytoprotective and anti-inflammatory effects of PAL31 overexpression in glial cells.
abstract: 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/IFNγ 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/IFNγ 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.
authors.forename: Fan-Wei
authors.initials: FW
authors.lastname: Tseng
authors.forename: Dann-Ying
authors.initials: DY
authors.lastname: Liou
authors.affiliation: Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan. mjtsai2@vghtpe.gov.tw.
authors.forename: May-Jywan
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Huang
authors.forename: Henrich
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D018832:Molecular Chaperones; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013124:Spinal Injuries / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: C412378:Anp32b protein, rat; D018797:Cell Cycle Proteins; D018832:Molecular Chaperones; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat