Overexpression of glia maturation factor in astrocytes leads to immune activation of microglia through secretion of granulocyte-macrophage-colony stimulating factor.

We infected a mixed culture of primary rat astrocytes and microglia with a replication-defective adenovirus carrying the rat glia maturation factor (GMF) cDNA. Affymetrix microarray analysis showed a big increase in the expression of several major histocompatibility complex (MHC) class II proteins along with interleukin-1beta (IL-1beta). Subsequent study using reverse transcription-polymerase chain reaction (RT-PCR) yielded the same results with the mixed culture, but not with pure astrocytes or pure microglia. We also noticed that the GMF/virus construct infected only astrocytes but not microglia. This led us to suspect that overexpression of GMF in astrocytes resulted in the secretion of an active substance that stimulated the microglia to express MHC II and IL-1beta. We identified this substance as granulocyte-macrophage-colony stimulating factor (GM-CSF). MHC II are unique to antigen-presenting cells such as microglia and monocytes. The results suggest that GMF in astrocytes can initiate a series of events, leading to immune activation in the nervous system, and implicates its involvement in autoimmune diseases such as multiple sclerosis.