title: Regulation of miR-24, miR-30b, and miR-142-3p during macrophage and dendritic cell differentiation potentiates innate immunity.
abstract: miRNAs are ubiquitous regulators of human biology. Parallel profiling of in vitro monocyte-to-Mφ and monocyte-to-DC differentiation revealed static, convergent, and divergent expression of miRNA. Bioinformatic and network analysis of differentially expressed miRNAs implicated miR-24, miR-30b, and miR-142-3p as negative regulators of intracellular signaling pathways, triggered not only by differentiation factors (M-CSF/GM-CSF/IL-4) but also from PRRs. Manipulation of miR-24, miR-30b, and miR-142-3p expression during the differentiation of mD-Mφ and mD-DC differentiation had minimal impact on the acquisition of phenotype but significantly abrogated the ability of these cells to mount inflammatory responses to pathogen-associated stimuli. Forced expression of these miRNAs, which are down-regulated during differentiation, inhibited release of inflammatory cytokines [TNF-α, IL-12(p40), IL-6] upon stimulation with LPS. Functional analysis revealed overlapping mechanisms of inhibition, including surface expression of TLR4/CD14/MD-1 and intracellular PKCα/NF-κB activation. Potential intermediary targets of the TLR4-NF-κB axis included members of the PI3K and MAPK families and PKC isoforms. These results demonstrate the requirement of miR-24, miR-30b, and miR-142-3p down-regulation for the generation of fully functional Mφs and DCs.
authors.affiliation: Department of Periodontics, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Jezrom B
authors.initials: JB
authors.lastname: Fordham
authors.affiliation: Department of Periodontics, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Afsar R
authors.initials: AR
authors.lastname: Naqvi
authors.affiliation: Department of Periodontics, University of Illinois at Chicago, Chicago, Illinois, USA snares@uic.edu.
authors.forename: Salvador
authors.initials: S
authors.lastname: Nares
mesh_terms: D002454:Cell Differentiation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: C508598:IL4 protein, human; C508600:IL6 protein, human; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D008070:Lipopolysaccharides; C555159:MIRN142 microRNA, human; C543845:MIRN24 microRNA, human; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: TLR; cytokine