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Reduced Severity of Experimental Autoimmune Encephalomyelitis in GMF-Deficient Mice

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Abstract

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-1β, and MIP-1β, 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.

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Fig. 1
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Abbreviations

GMF:

Glia maturation factor

GM-CSF:

Granulocyte-macrophage-colony stimulating factor

TNF:

Tumor necrosis factor

RANTES:

Regulated upon activation, normal T cell expressed and secreted

MCP-1:

Monocyte chemoattractant protein-1

IP-10:

Interferon-inducible 10-kDa protein

INOS:

Inducible nitric oxide synthase

RT-PCR:

Reverse transcription-polymerase chain reaction

ELISA:

Enzyme-linked immunosorbent assay

MS:

Multiple sclerosis

EAE:

Experimental autoimmune encephalomyelitis

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Acknowledgments

We thank Houdy Khosravi, Kiwhoon Lee, Coletta Sanchez Warner, Amanda Alexander and Ashna Zaheer for excellent technical assistance. We thank Dr Joseph Francis, Dr Don Bonthius and Dr Satya Mathur for help in preparation of Fig. 2. GMF-deficient mice were produced at the University of Iowa Gene Targeting Core Facility. This work was supported by the Department of Veterans Affairs Merit Review award (to A.Z.) and by the National Institute of Neurological Disorders and Stroke grant NS-47145 (to A.Z.).

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Authors and Affiliations

  1. Veterans Affair Medical Center, Iowa City, IA, USA

    Asgar Zaheer

  2. Division of Neurochemistry and Neurobiology, Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA

    Asgar Zaheer, Smita Zaheer, Shailendra K. Sahu & Ramon Lim

  3. Department of Neurosurgery, University of Iowa, Iowa City, IA, 52242, USA

    Shailendra K. Sahu

  4. Department of Obstetric and Gynecology, University of Iowa, Iowa City, IA, 52242, USA

    Baoli Yang

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  1. Asgar Zaheer
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  2. Smita Zaheer
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  5. Ramon Lim
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Correspondence to Asgar Zaheer.

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Zaheer, A., Zaheer, S., Sahu, S.K. et al. Reduced Severity of Experimental Autoimmune Encephalomyelitis in GMF-Deficient Mice. Neurochem Res 32, 39–47 (2007). https://doi.org/10.1007/s11064-006-9220-x

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  • DOI: https://doi.org/10.1007/s11064-006-9220-x

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