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Thromb Haemost. 2015 Mar;113(3):473-81. doi: 10.1160/TH14-06-0507. Epub 2015 Jan 15.

Regulation of monocyte/macrophage polarisation by extracellular RNA.

Author information

1
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.
2
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.

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.

KEYWORDS:

Extracellular RNA; gene expression; inflammation; microarray technology; monocyte/macrophage polarisation

PMID:
25589344
PMCID:
PMC4427572
DOI:
10.1160/TH14-06-0507
[Indexed for MEDLINE]
Free PMC Article

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