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. In this present investigation, using GMF-deficient mice, we study the role of GMF and how the lack of GMF affects the EAE disease. Our results show a significant decrease in incidence, delay in onset, and reduced severity of EAE in GMF-deficient mice, and support the hypothesis that GMF plays a major role in the pathogenesis of disease.
Zaheer
Asgar
A
Veterans Affair Medical Center, Iowa City, IA, USA. asgar-zaheer@uiowa.edu
Zaheer
Smita
S
Sahu
Shailendra K
SK
Yang
Baoli
B
Lim
Ramon
R
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology*; D005260:Female; D020904:Glia Maturation Factor / Q000172:deficiency*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010446:Peptide Fragments / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D020904:Glia Maturation Factor; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse