title: Regulation of monocyte/macrophage polarisation by extracellular RNA.
abstract: Monocytes/macrophages respond to external stimuli with rapid changes in the expression of numerous inflammation-related genes to undergo polarisation towards the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype. We have previously shown that, independently of Toll-like receptor activation, extracellular RNA (eRNA) could exert pro-thrombotic and pro-inflammatory properties in the cardiovascular system to provoke cytokine mobilisation. Here, mouse bone marrow-derived-macrophages (BMDM) differentiated with mouse macrophage-colony-stimulating factor (M-CSF) were found to be skewed towards the M1 phenotype when exposed to eRNA. This resulted in up-regulated expression of inflammatory markers such as Tnf-α and Il-6, together with Il-12 and iNOS, whereas anti-inflammatory genes such as chitinase-like proteins (Ym1/2) and macrophage mannose receptor-2 (Cd206) were significantly down-regulated. Human peripheral blood monocytes were treated with eRNA and analysed by micro-array analysis of the whole human genome, revealing an up-regulation of 79 genes by at least four-fold; 27 of which are related to signal transduction and 15 genes associated with inflammatory response. In accordance with the proposed actions of eRNA as a pro-inflammatory "alarm signal", these data shed light on the role of eRNA in the context of chronic inflammatory diseases such as atherosclerosis.
authors.forename: Hector A
authors.initials: HA
authors.lastname: Cabrera-Fuentes
authors.forename: Mercedes L
authors.initials: ML
authors.lastname: Lopez
authors.forename: Sara
authors.initials: S
authors.lastname: McCurdy
authors.forename: Silvia
authors.initials: S
authors.lastname: Fischer
authors.forename: Svenja
authors.initials: S
authors.lastname: Meiler
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Baumer
authors.forename: Sebastian P
authors.initials: SP
authors.lastname: Galuska
authors.affiliation: Klaus T. Preissner, PhD, Depart. Biochemistry, Medical School, Justus-Liebig-University, Friedrichstrasse 24, 35392 Giessen, Germany, Tel.: +49 641 994 7500, e-mail: klaus.t.preissner@biochemie.med.uni-giessen.de.
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.affiliation: William A. Boisvert, PhD, Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, BSB 311C, Honolulu, HI 96813, USA, Tel.: + 1 808 692 1567, E-mail: wab@hawaii.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Boisvert
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D012313:RNA / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D012313:RNA
keywords: Extracellular RNA; gene expression; inflammation; microarray technology; monocyte/macrophage polarisation