Diminished cytokine and chemokine expression in the central nervous system of GMF-deficient mice with experimental autoimmune encephalomyelitis.
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.
Zaheer
Asgar
A
Veterans Affair Medical Center, Iowa City, IA 52242, USA. asgar-zaheer@uiowa.edu
Sahu
Shailendra K
SK
Wu
Yanghong
Y
Zaheer
Ashna
A
Haas
Joel
J
Lee
Kiwhoon
K
Yang
Baoli
B
D000704:Analysis of Variance; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D020904:Glia Maturation Factor / Q000172:deficiency*; D006023:Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D018925:Chemokines; D016207:Cytokines; D020904:Glia Maturation Factor; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; C445081:myelin oligodendrocyte glycoprotein (35-55)