title: Silencing of microRNA-155 in mice during acute inflammatory response leads to derepression of c/ebp Beta and down-regulation of G-CSF.
abstract: microRNA-155 (miR-155) has been implicated as a central regulator of the immune system, but its function during acute inflammatory responses is still poorly understood. Here we show that exposure of cultured macrophages and mice to lipopolysaccharide (LPS) leads to up-regulation of miR-155 and that the transcription factor c/ebp Beta is a direct target of miR-155. Interestingly, expression profiling of LPS-stimulated macrophages combined with overexpression and silencing of miR-155 in murine macrophages and human monocytic cells uncovered marked changes in the expression of granulocyte colony-stimulating factor (G-CSF), a central regulator of granulopoiesis during inflammatory responses. Consistent with these data, we show that silencing of miR-155 in LPS-treated mice by systemically administered LNA-antimiR results in derepression of the c/ebp Beta isoforms and down-regulation of G-CSF expression in mouse splenocytes. Finally, we report for the first time on miR-155 silencing in vivo in a mouse inflammation model, which underscores the potential of miR-155 antagonists in the development of novel therapeutics for treatment of chronic inflammatory diseases.
authors: Santaris Pharma, Kogle Allé 6, DK-2970 Hørsholm, Denmark.
authors: Jesper
authors: J
authors: Worm
authors: Jan
authors: J
authors: Stenvang
authors: Andreas
authors: A
authors: Petri
authors: Klaus Stensgaard
authors: KS
authors: Frederiksen
authors: Susanna
authors: S
authors: Obad
authors: Joacim
authors: J
authors: Elmén
authors: Maj
authors: M
authors: Hedtjärn
authors: Ellen Marie
authors: EM
authors: Straarup
authors: Jens Bo
authors: JB
authors: Hansen
authors: Sakari
authors: S
authors: Kauppinen
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D008070:Lipopolysaccharides; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D020033:Protein Isoforms; D016179:Granulocyte Colony-Stimulating Factor