MicroRNA-181b Regulates ALX/FPR2 Receptor Expression and Proresolution Signaling in Human Macrophages

作者：Pierdomenico Anna Maria; Recchiuti Antonio; Simiele Felice; Codagnone Marilina; Mari Veronica Cecilia; Davi Giovanni; Romano Mario^*

来源：Journal of Biological Chemistry, 2015, 290(6): 3592-3600.

DOI：10.1074/jbc.M114.592352

Regulatory mechanisms of ALX/FPR2, the lipoxin A(4) receptor, expression have considerable relevance in inflammation resolution. Because microRNAs (miRs) are emerging as key players in inflammation resolution, here we examined microRNA-mediated regulation of ALX/FPR2 (lipoxin A4 receptor/formyl peptide receptor 2) 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 down-regulated ALX/FPR2 protein levels (-25%), whereas miR-181b knockdown gave a significant increase in ALX/FPR2 (+60%). miR-181b levels decreased during monocyte to macrophage differentiation (-50%), whereas ALX/FPR2 expression increased significantly (+60%). miR-181b overexpression blunted lipoxin A(4) (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 proresolution responses mediated by miR-181b, thus uncovering novel components of the endogenous inflammation resolution circuits.

• 出版日期2015-2-6