Thromb Haemost 2015; 113(03): 473-481
DOI: 10.1160/TH14-06-0507
Theme Issue Article
Schattauer GmbH

Regulation of monocyte/macrophage polarisation by extracellular RNA

Hector A. Cabrera-Fuentes
1   Institute of Biochemistry, Medical School, Justus-Liebig University, Giessen, Germany
2   Department of Microbiology, Kazan Federal University, Kazan, Russian Federation
,
Mercedes L. Lopez
3   Instituto Venezolano de Investigaciones Cientficas, Centro de Biofísica y Bioquímica, Caracas, Venezuela
,
Sara McCurdy
4   Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA;
,
Silvia Fischer
1   Institute of Biochemistry, Medical School, Justus-Liebig University, Giessen, Germany
,
Svenja Meiler
5   Department of Medical Biochemistry, Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Yvonne Baumer
4   Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA;
,
Sebastian P. Galuska
1   Institute of Biochemistry, Medical School, Justus-Liebig University, Giessen, Germany
,
Klaus T. Preissner
1   Institute of Biochemistry, Medical School, Justus-Liebig University, Giessen, Germany
2   Department of Microbiology, Kazan Federal University, Kazan, Russian Federation
,
William A. Boisvert
2   Department of Microbiology, Kazan Federal University, Kazan, Russian Federation
4   Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA;
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Publikationsverlauf

Received: 10. Juni 2014

Accepted after major revision: 28. Januar 2014

Publikationsdatum:
29. November 2017 (online)

Summary

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 (antiinflammatory) phenotype. We have previously shown that, independently of Toll-like receptor activation, extracellular RNA (eRNA) could exert prothrombotic 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.

Drs Preissner and Boisvert contributed equally to this work as senior authors.


 
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