MicroRNA-181b Regulates ALX/FPR2 Receptor Expression and Proresolution Signaling in Human Macrophages
| Autor: | Giovanni Davì, Anna M Pierdomenico, Felice Simiele, Mario R. Romano, Antonio Recchiuti, Veronica Cecilia Mari, Marilina Codagnone |
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| Rok vydání: | 2015 |
| Předmět: |
Docosahexaenoic Acids
Receptor expression Inflammation Biology Biochemistry Formyl peptide receptor 2 Phagocytosis medicine Humans Receptors Lipoxin 3' Untranslated Regions Molecular Biology Regulation of gene expression Gene knockdown Macrophages Monocyte Cell Biology Lipid signaling Receptors Formyl Peptide Lipids Cell biology Lipoxins MicroRNAs medicine.anatomical_structure lipids (amino acids peptides and proteins) medicine.symptom Signal transduction Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 290:3592-3600 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m114.592352 |
| Popis: | Regulatory mechanisms of ALX/FPR2, the lipoxin A4 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 A4 (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. |
| Databáze: | OpenAIRE |
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