Neuroprotective effects of G-CSF administration in microglia-mediated reactive T cell activation in vitro.

Abstract

G-CSF is a growth factor that has known neuroprotective effects in a variety of experimental brain injury models. As both antigen-presenting microglia and reactive T cells are key components in the development and progression of EAE, the aim of this study is to investigate the neuroprotective effects of recombinant human G-CSF, as administered in microglia-mediated reactive T cell assay in vitro. Our results indicate that G-CSF treatment has no apparent effect for the resting un-activated microglia. G-CSF pre-protection of microglia increased protective cytokine IL-4 production and effectively inhibited the productions of NO and other inflammatory mediators (IFN-γ, TNF-α, IL-1β, IL-17, and chemokine MCP-1) after LPS stimulation. G-CSF suppressed the proliferative response of microglia-mediated MOG35-55 reactive T cells. G-CSF-microglia-T cells increased IL-4 and IL-10 secretions and decreased IFN-γ, TNF-α, and IL-17 productions. G-CSF significantly elevated CD4+CD25+ regulatory T cell subset in microglia-mediated reactive T cells. Moreover, G-CSF inhibited MHC-II expression of microglia after LPS activation or in the interactions of microglia and reactive T cells. G-CSF administration induced the apoptosis and enhanced the G0/G1 to S phase transition and elevated the gene expression of apoptosis markers in microglia-mediated reactive T cells after stimulated by specific antigen MOG35-55. These findings reveal that G-CSF administration potently neuroprotects the central nervous system (CNS) from immune-mediated damage in microglia-mediated reactive T cell activation. Apoptosis of reactive T cells in CNS is important in attenuating the development of autoimmune CNS diseases. G-CSF administration has neuroprotective effects in CNS and the potential to be a therapeutic agent in multiple sclerosis.