Neurochemical Research

, Volume 32, Issue 12, pp 2123–2131 | Cite as

Glia Maturation Factor Regulation of STAT Expression: A Novel Mechanism in Experimental Autoimmune Encephalomyelitis

  • Smita Zaheer
  • Yanghong Wu
  • Jon Bassett
  • Baoli Yang
  • Asgar Zaheer
Original Paper

Abstract

Inflammatory cytokines are implemented in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We previously demonstrated that glia maturation factor (GMF), a brain protein, isolated, sequenced and cloned in our laboratory, induce expression of proinflammatory cytokine/chemokine in the central nervous system (CNS). We found GMF-deficient (knockout) mice relatively resistant to EAE development after immunization with encephalitogenic MOG peptide 35–55. Consistent with these findings, the expression of proinflammatory cytokines in CNS of mice with EAE differed profoundly between wild type and GMF-knockout mice. In the present study we examined the expressions of six murine signal transducers and activators of transcription (STATs) genes, which are known to regulate the cytokine-dependent signal transduction pathways in autoimmune inflammation. The expressions of STATs genes were evaluated in the brains and spinal cords of wild type and GMF-knockout mice at the peak of EAE by quantitative real-time RT-PCR. Compared to GMF-knockout mice, the expressions of STAT1, STAT2, STAT3, STAT4, STAT5, and STAT6 genes were significantly (P < 0.001) upregulated in the wild type mice exhibiting EAE symptoms. The results are consistent with the diminished development of EAE in the GMF-knockout mice. A significant suppression of STATs expression in GMF-knockout mice suggests GMF as an upstream effector of JAK/STAT signaling.

Keywords

Glia maturation factor (GMF) Experimental autoimmune encephalomyelitis (EAE) Multiple sclerosis (MS) Signal transducers and activators of transcription (STAT) Myelin oligodendrocyte glycoprotein (MOG) 

Abbreviations

GMF

Glia maturation factor

RT-PCR

Reverse transcription-polymerase chain reaction

ELISA

Enzyme-linked immunosorbent assay

STAT

Signal transducers and activators of transcription

MOG

Myelin oligodendrocyte glycoprotein

MS

Multiple sclerosis

EAE

Experimental autoimmune encephalomyelitis

Notes

Acknowledgements

We thank Shailendra Sahu, Marcus Ahrens, Ashna Zaheer, Scott Knight, Satya Mathur and Krishnakumar Menon for excellent technical help. 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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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Smita Zaheer
    • 3
  • Yanghong Wu
    • 2
  • Jon Bassett
    • 1
    • 2
  • Baoli Yang
    • 3
  • Asgar Zaheer
    • 1
    • 2
  1. 1.Veterans Affair Medical CenterIowa CityUSA
  2. 2.Division of Neurochemistry and Neurobiology, Department of NeurologyUniversity of IowaIowa CityUSA
  3. 3.Department of Obstetric and GynecologyUniversity of IowaIowa CityUSA

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