MicroRNA-181b regulates ALX/FPR2 expression and proresolution signaling in human macrophages [Cell Biology]

December 11th, 2014 by Pierdomenico, A. M., Recchiuti, A., Simiele, F., Codagnone, M., Mari, V. C., Davi, G., Romano, M.

Regulatory mechanisms of ALX/FPR2, the lipoxin (LX)A4 receptor, expression have considerable relevance in inflammation resolution. Since microRNAs (miRs) are emerging as key players in inflammation resolution, here we examined microRNA-mediated regulation of ALX/FPR2 expression. By matching data from bioinformatic algorithms, we found 27 miRs predicted to bind the 3′UTR of ALX/FPR2. Among these, we selected miR-181b because of its link with inflammation. Using a luciferase reporter system, we assessed miR-181b binding to ALX/FPR2 3′UTR. Consistent with this, miR-181b overexpression in human macrophages significantly downregulated ALX/FPR2 protein levels (- 25 %), whereas miR-181b knock-down gave a significant increase in ALX/FPR2 (+ 60 %). miR-181b levels decreased during monocyte to macrophage differentiation (- 50 %), while ALX/FPR2 expression increased significantly (+ 60 %). miR-181b overexpression blunted LXA4- (0.1-10 nM) and Resolvin D1- (0.01-10 nM) stimulated phagocytic activity of macrophages. These results unravel novel regulatory mechanisms of ALX/FPR2 expression and ligand-evoked macrophages pro-resolutive responses mediated by miR-181b, thus uncovering novel components of the endogenous inflammation resolution circuits.