[HTML][HTML] MicroRNAs in resolution of acute inflammation: identification of novel resolvin D1-miRNA circuits

A Recchiuti, S Krishnamoorthy, G Fredman… - The FASEB …, 2011 - ncbi.nlm.nih.gov
The FASEB Journal, 2011ncbi.nlm.nih.gov
Mechanisms controlling resolution of acute inflammation are of wide interest. Here, we
investigated microRNAs (miRNAs) in self-limited acute inflammatory exudates and their
regulation by resolvin D1 (RvD1). Using real-time PCR analysis, we found in resolving
exudates that miR-21, miR-146b, miR-208a, miR-203, miR-142, miR-302d, and miR-219
were selectively regulated (P< 0.05) in self-limited murine peritonitis. RvD1 (300 ng/mouse
or 15 μg kg− 1) reduced zymosan-elicited neutrophil infiltration into the peritoneum 25–50 …
Abstract
Mechanisms controlling resolution of acute inflammation are of wide interest. Here, we investigated microRNAs (miRNAs) in self-limited acute inflammatory exudates and their regulation by resolvin D1 (RvD1). Using real-time PCR analysis, we found in resolving exudates that miR-21, miR-146b, miR-208a, miR-203, miR-142, miR-302d, and miR-219 were selectively regulated (P< 0.05) in self-limited murine peritonitis. RvD1 (300 ng/mouse or 15 μg kg− 1) reduced zymosan-elicited neutrophil infiltration into the peritoneum 25–50% and shortened the resolution interval (R i) by∼ 4 h. In peritonitis at 12 h, RvD1 up-regulated miR-21, miR-146b, and miR-219 and down-regulated miR-208a in vivo. In human macrophages overexpressing recombinant RvD1 receptors ALX/FPR2 or GPR32, these same miRNAs were significantly regulated (P< 0.05) by RvD1 at concentrations as low as 10 nM, recapitulating the in vivo circuit. In addition, RvD1-miRNAs identified herein target cytokines and proteins involved in the immune system, eg, miR-146b targeted NF-κB signaling, and miR-219 targeted 5-lipoxygenase and reduced leukotriene production. RvD1 also reduced nuclear translocation of NF-κB and SMAD and down-regulated phospho-IκB. Taken together, these results indicate that resolvin-regulated specific miRNAs target genes involved in resolution and establish a novel resolution circuit involving RvD1 receptor-dependent regulation of specific miRNAs.—Recchiuti, A., Krishnamoorthy, S., Fredman, G., Chiang, N., and Serhan, CN MicroRNAs in resolution of acute inflammation: identification of novel resolvin D1-miRNA circuits.
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