Glia maturation factor regulation of STAT expression: a novel mechanism in experimental autoimmune encephalomyelitis.
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.
Zaheer
Smita
S
Veterans Affairs Medical Center, Iowa City, IA, USA. asgar-zaheer@uiowa.edu
Wu
Yanghong
Y
Bassett
Jon
J
Yang
Baoli
B
Zaheer
Asgar
A
D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D020904:Glia Maturation Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D047468:Immunoprecipitation; D053612:Janus Kinases / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000276:immunology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000502:physiology
D016207:Cytokines; D020904:Glia Maturation Factor; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases