A novel role of glia maturation factor: induction of granulocyte-macrophage colony-stimulating factor and pro-inflammatory cytokines.

The glia maturation factor (GMF), which was discovered in our laboratory, is a highly conserved protein predominantly localized in astrocytes. GMF is an intracellular regulator of stress-related signal transduction. We now report that the overexpression of GMF in astrocytes leads to the destruction of primary oligodendrocytes by interactions between highly purified cultures of astrocytes, microglia, and oligodendrocytes.

Reduced severity of experimental autoimmune encephalomyelitis in GMF-deficient mice.

Glia maturation factor (GMF), a highly conserved brain-specific protein, isolated, sequenced and cloned in our laboratory. Overexpression of GMF in astrocytes induces the production and secretion of granulocyte-macrophage-colony stimulating factor (GM-CSF), and subsequent immune activation of microglia, expression of several proinflammatory genes including major histocompatibility complex proteins, IL-1beta, and MIP-1beta, all associated with the development of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. Based on GMF's ability to activate microglia and induce well-established proinflammatory mediators, including GM-CSF, we hypothesize that GMF is involved in the pathogenesis of inflammatory disease EAE.

GMF-knockout mice are unable to induce brain-derived neurotrophic factor after exercise.

We earlier reported that overexpression of glia maturation factor (GMF) in cultured astrocytes enhances the production of brain-derived neurotrophic factor (BDNF). The current study was conducted to find out whether BDNF production is impaired in animals devoid of GMF. To this end GMF-knockout (KO) mice were subjected to exercise and the neurotrophin mRNAs were determined by real-time RT-PCR.

Impaired motor performance and learning in glia maturation factor-knockout mice.

Glia maturation factor (GMF) is a unique brain protein localized in astrocytes and some neuronal populations. Studies with overexpression of GMF using adenovirus vector have uncovered its regulatory role in intracellular signal transduction and downstream induction of biologically active molecules, including the neurotrophins and cytokines. The current paper deals with the behavior of mice devoid of GMF protein (knockout).

Decreased copper-zinc superoxide dismutase activity and increased resistance to oxidative stress in glia maturation factor-null astrocytes.

Glia maturation factor (GMF) is a highly conserved protein found mainly in the nervous system. The current work was undertaken to investigate the effect of GMF expression in astrocytes on CuZn superoxide dismutase (CuZnSOD or SOD I) and on the vulnerability of the cells to H2O2 toxicity. Primary astrocyte cultures were derived from mice in which the GMF gene was completely deleted by homologous recombination (knockout).

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.