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.
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Authors | Asgar Zaheer, Shailendra K Sahu, Yanghong Wu, Ashna Zaheer, Joel Haas, Kiwhoon Lee, Baoli Yang |
Journal | Brain research
(Brain Res)
Vol. 1144
Pg. 239-47
(May 04 2007)
ISSN: 0006-8993 [Print] Netherlands |
PMID | 17316572
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Chemokines
- Cytokines
- Glia Maturation Factor
- Glycoproteins
- Myelin-Oligodendrocyte Glycoprotein
- Peptide Fragments
- RNA, Messenger
- myelin oligodendrocyte glycoprotein (35-55)
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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)
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