title: MicroRNA-181b regulates ALX/FPR2 receptor expression and proresolution signaling in human macrophages.
abstract: 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.
authors.affiliation: From the Department of Medicine and Aging Sciences and Center of Excellence on Aging "G. D'Annunzio" University Foundation, 66013 Chieti, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Pierdomenico
authors.affiliation: Center of Excellence on Aging "G. D'Annunzio" University Foundation, 66013 Chieti, Italy Department of Medical, Oral, and Technological Sciences, "G. d'Annunzio" University, 66013 Chieti, Italy and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Recchiuti
authors.affiliation: Center of Excellence on Aging "G. D'Annunzio" University Foundation, 66013 Chieti, Italy Department of Medical, Oral, and Technological Sciences, "G. d'Annunzio" University, 66013 Chieti, Italy and.
authors.forename: Felice
authors.initials: F
authors.lastname: Simiele
authors.affiliation: Center of Excellence on Aging "G. D'Annunzio" University Foundation, 66013 Chieti, Italy Department of Medical, Oral, and Technological Sciences, "G. d'Annunzio" University, 66013 Chieti, Italy and.
authors.forename: Marilina
authors.initials: M
authors.lastname: Codagnone
authors.affiliation: Center of Excellence on Aging "G. D'Annunzio" University Foundation, 66013 Chieti, Italy Department of Medical, Oral, and Technological Sciences, "G. d'Annunzio" University, 66013 Chieti, Italy and.
authors.forename: Veronica Cecilia
authors.initials: VC
authors.lastname: Mari
authors.affiliation: From the Department of Medicine and Aging Sciences and Center of Excellence on Aging "G. D'Annunzio" University Foundation, 66013 Chieti, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
authors.affiliation: Center of Excellence on Aging "G. D'Annunzio" University Foundation, 66013 Chieti, Italy Department of Medical, Oral, and Technological Sciences, "G. d'Annunzio" University, 66013 Chieti, Italy and mromano@unich.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Romano
mesh_terms: D020413:3' Untranslated Regions; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D006801:Humans; D044045:Lipoxins / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; C105101:FPR2 protein, human; D044045:Lipoxins; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C518399:resolvin D1; D004281:Docosahexaenoic Acids
keywords: Eicosanoid; G Protein-coupled Receptor (GPCR); Gene Regulation; Inflammation; Lipid Signaling; Macrophage; MicroRNA (miRNA)