HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Diminished cytokine and chemokine expression in the central nervous system of GMF-deficient mice with experimental autoimmune encephalomyelitis.

Abstract
Pro-inflammatory cytokines/chemokines are implemented in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model with clinical and pathological similarities to multiple sclerosis. We have previously shown that over-expression of glia maturation factor (GMF) in glial cells cause excessive production and secretion of pro-inflammatory cytokines/chemokines sufficient to destroy the myelin-forming oligodendroglial cell in vitro. In this present investigation, we evaluate the expression of pro-inflammatory mediators in the central nervous system (CNS) of GMF+/+ (wild type) mice and GMF-/- (GMF-knockout) mice at the peak of EAE induced by immunization with MOG 35-55 peptide. GMF+/+ (Wt) mice developed severe EAE with a maximal mean clinical score of 3.6+/-0.5 by day 16 post-immunization, whereas GMF-KO mice showed significantly delayed EAE with an average onset on day 26 pi with reduced mean clinical score of 1.3+/-0.3. Three of fifteen Wt mice as compared to none of GMF-KO mice died of EAE. Encephalitogenic cells from Wt mice transferred to recipient GMF-KO mice caused very mild and with low incidence of EAE. We determined the differences in the expression of cytokines, IFN-gamma, TNF-alpha, IL-1 beta, IL-6, IL-4, IL-10, and chemokines, MIP-1, MIP-2, IP-10, MCP-1, GM-CSF mRNA by quantitative real-time RT-PCR in brain and spinal cord. Our results demonstrate significantly low levels of pro-inflammatory cytokines/chemokines in the CNS of GMF-KO mice and increased expression in Wt mice with EAE. Our data suggest that GMF play a critical role in CNS inflammation.
AuthorsAsgar Zaheer, Shailendra K Sahu, Yanghong Wu, Ashna Zaheer, Joel Haas, Kiwhoon Lee, Baoli Yang
JournalBrain research (Brain Res) Vol. 1144 Pg. 239-47 (May 04 2007) ISSN: 0006-8993 [Print] Netherlands
PMID17316572 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Chemokines
  • Cytokines
  • Glia Maturation Factor
  • Glycoproteins
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • RNA, Messenger
  • myelin oligodendrocyte glycoprotein (35-55)
Topics
  • Analysis of Variance
  • Animals
  • Central Nervous System (metabolism)
  • Chemokines (metabolism)
  • Cytokines (metabolism)
  • Encephalomyelitis, Autoimmune, Experimental (chemically induced, genetics, pathology, physiopathology)
  • Enzyme-Linked Immunosorbent Assay (methods)
  • Gene Expression Regulation (genetics, physiology)
  • Glia Maturation Factor (deficiency)
  • Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • RNA, Messenger (biosynthesis)
  • Reverse Transcriptase Polymerase Chain Reaction (methods)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: