title: miR-24, miR-30b, and miR-142-3p regulate phagocytosis in myeloid inflammatory cells.
abstract: Micro-RNAs (miRNAs) are small noncoding RNAs that regulate various biological pathways. As their role in phagocytosis remains poorly understood, we investigated their impact on phagocytosis in myeloid inflammatory cells. Seven miRNAs (miR-24, -30b, -101, 142-3p, -652-3p, -652-5p, and -1275) that were differentially expressed during monocyte to macrophage (Mφ) and monocyte to dendritic cell (DC) differentiation were screened for their potential role in phagocytosis. Among these, overexpression of miR-24, miR-30b, and miR-142-3p in human monocyte-derived Mφ, DC, monocytes, and PBMCs significantly attenuate phagocytosis of Escherichia coli and Staphylococcus aureus, as well as the secretion of inflammatory mediators, including TNF-α, IL-6, and IL-12p40. miRNA-mediated changes in cytokine profiles were observed at transcriptional and/or posttranscriptional levels and importantly exhibit miRNA-specific impact. To examine the underlying mechanism, we monitored the expression of phagocytosis pathway-associated genes and identified several genes that were altered in Mφ and DC transfected with miR-24, miR-30b, and miR-142-3p mimics. Some of these genes with altered expression also harbor putative miRNA binding sites. We show that miR-142-3p directly regulates protein kinase Cα (PKCα), a key gene involved in phagocytosis. Interestingly, miR-142-3p and PKCα exhibit antagonistic expression during Mφ and DC differentiation. Short interfering RNA-mediated knockdown of PKCα in Mφ leads to reduced bacterial uptake, further highlighting the role of the gene in phagocytosis. Overall, these results demonstrate that miR-24, miR-30b, and miR-142-3p regulate phagocytosis and associated cytokine production in myeloid inflammatory cells through modulation of various genes involved in the pathway.
authors.affiliation: Department of Periodontics, University of Illinois at Chicago, Chicago, IL 60612.
authors.forename: Afsar Raza
authors.initials: AR
authors.lastname: Naqvi
authors.affiliation: Department of Periodontics, University of Illinois at Chicago, Chicago, IL 60612.
authors.forename: Jezrom B
authors.initials: JB
authors.lastname: Fordham
authors.affiliation: Department of Periodontics, University of Illinois at Chicago, Chicago, IL 60612 snares@uic.edu.
authors.forename: Salvador
authors.identifier: http://orcid.org/0000-0002-2194-1374
authors.initials: S
authors.lastname: Nares
mesh_terms: D015153:Blotting, Western; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D035683:MicroRNAs / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology*; D010587:Phagocytosis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D016207:Cytokines; C555159:MIRN142 microRNA, human; C543845:MIRN24 microRNA, human; C546086:MIRN30b microRNA, human; D035683:MicroRNAs