title: Strawberry notch homolog 2 is a novel inflammatory response factor predominantly but not exclusively expressed by astrocytes in the central nervous system.
abstract: Interleukin-6 (IL-6) participates in the host response to injury and infection in the central nervous system (CNS). We identified strawberry notch homolog 2 (Sbno2) as an IL-6-stimulated gene in murine astrocytes. Sbno2 is a mouse homolog of the sno gene in Drosophila but little is known about the regulation or function of the mammalian gene. Here we examined the regulation of the Sbno2 gene in astrocytes in vitro and in the murine CNS following systemic endotoxin administration. In murine and human cultured astrocytes, Sbno2 gene expression was significantly upregulated in a dose- and time-dependent fashion by hyper-IL-6 (IL-6 + soluble IL-6 receptor). The level of Sbno2 mRNA was also upregulated significantly in murine astrocytes by other glycoprotein130 cytokine-family members and the pro-inflammatory cytokines interleukin-1 beta and tumor necrosis factor alpha. These changes were reflected by corresponding alterations in the level of the SBNO2 protein. Inhibiting protein synthesis resulted in higher Sbno2 mRNA and did not abolish the upregulation of Sbno2 mRNA mediated by hyper-IL-6. Inhibition of transcription led to a rapid reduction in hyper-IL-6-induced Sbno2 mRNA in astrocytes suggesting that the Sbno2 mRNA is quite unstable. Following intra-peritoneal lipopolysaccharide injection in mice, Sbno2 mRNA levels in the brain were significantly increased. Cellular localization studies revealed that this increase in Sbno2 mRNA occurred predominantly in astrocytes and in the choroid plexus and in some microglia, endothelial cells, and neurons. These findings are consistent with SBNO2 functioning as an acute inflammatory response gene in astrocytes as well as other cells in the CNS.
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.|Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Grill
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Taylor E
authors.initials: TE
authors.lastname: Syme
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Aline L
authors.initials: AL
authors.lastname: Noçon
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Andy Z X
authors.initials: AZ
authors.lastname: Lu
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Dale
authors.initials: D
authors.lastname: Hancock
authors.affiliation: Department of Biochemistry, University of Kiel, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, Australia.
authors.forename: Iain L
authors.initials: IL
authors.lastname: Campbell
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D012097:Repressor Proteins; C526192:SBNO2 protein, mouse; C456339:cytokine receptor, GLM-R; D003513:Cycloheximide
keywords: astrocyte; cytokines; glycoprotein 130; inflammation; strawberry notch homolog 2