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2015 ; 113
(3
): 473-81
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Regulation of monocyte/macrophage polarisation by extracellular RNA
#MMPMID25589344
Cabrera-Fuentes HA
; Lopez ML
; McCurdy S
; Fischer S
; Meiler S
; Baumer Y
; Galuska SP
; Preissner KT
; Boisvert WA
Thromb Haemost
2015[Mar]; 113
(3
): 473-81
PMID25589344
show ga
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-? 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.
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