Reduced severity of experimental autoimmune encephalomyelitis in GMF-deficient mice

• Published in: Neurochemical research 2007-01, Vol.32 (1), p.39-47
• Main Authors: Zaheer, Asgar, Zaheer, Smita, Sahu, Shailendra K, Yang, Baoli, Lim, Ramon
• Format: Article
• Language: English
• Subjects: Animals; Encephalomyelitis, Autoimmune, Experimental - physiopathology; Female; Glia Maturation Factor - deficiency; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Mice; Mice, Knockout; Myelin Proteins; Myelin-Associated Glycoprotein - immunology; Myelin-Oligodendrocyte Glycoprotein; Nitric Oxide Synthase Type II - biosynthesis; Peptide Fragments - pharmacology; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-006-9220-x

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.