Diminished Cytokine and Chemokine Expression in the Central Nervous System of Gmf-deficient Mice with Experimental Autoimmune Encephalomyelitis.
From: Veterans Affair Medical Center, Iowa City, IA 52242, USA. asgar-zaheer@uiowa.edu
Brain research
- Publish Date: May 2007
- ISSN: 0006-8993
- Volume: 1144
- Issue:
- Pages: 239-47
- Medium: Print
- Language: English
- Citation (JAMA): Zaheer Asgar, Sahu Shailendra K, Wu Yanghong, et al. Diminished Cytokine and Chemokine Expression in the Central Nervous System of Gmf-deficient Mice with Experimental Autoimmune Encephalomyelitis.. Brain Res. May 2007;1144:239-47
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.
Mesh Headings (Keywords): Analysis of Variance, Animals, Central Nervous System, Chemokines, Cytokines, Encephalomyelitis, Autoimmune, Experimental, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Glia Maturation Factor, Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Peptide Fragments, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction
Check for Full Text / PubMed Unique Identifier (PMID): 17316572
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