title: Glia maturation factor regulation of STAT expression: a novel mechanism in experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Veterans Affairs Medical Center, Iowa City, IA, USA. asgar-zaheer@uiowa.edu
authors.forename: Smita
authors.initials: S
authors.lastname: Zaheer
authors.forename: Yanghong
authors.initials: Y
authors.lastname: Wu
authors.forename: Jon
authors.initials: J
authors.lastname: Bassett
authors.forename: Baoli
authors.initials: B
authors.lastname: Yang
authors.forename: Asgar
authors.initials: A
authors.lastname: Zaheer
mesh_terms: 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
chemical_list: D016207:Cytokines; D020904:Glia Maturation Factor; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases