title: MicroRNA expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal miR-511 as putative positive regulator of Toll-like receptor 4.
abstract: Dendritic cells (DCs) and macrophages (MFs) are important multifunctional immune cells. Like other cell types, they express hundreds of different microRNAs (miRNAs) that are recently discovered post-transcriptional regulators of gene expression. Here we present updated miRNA expression profiles of monocytes, DCs and MFs. Compared with monocytes, ∼50 miRNAs were found to be differentially expressed in immature and mature DCs or MFs, with major expression changes occurring during the differentiation. Knockdown of DICER1, a protein needed for miRNA biosynthesis, led to lower DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and enhanced CD14 protein levels, confirming the importance of miRNAs in DC differentiation in general. Inhibition of the two most highly up-regulated miRNAs, miR-511 and miR-99b, also resulted in reduced DC-SIGN level. Prediction of miRNA-511 targets revealed a number of genes with known immune functions, of which TLR4 and CD80 were validated using inhibition of miR-511 in DCs and luciferase assays in HEK293 cells. Interestingly, under the cell cycle arrest conditions, miR-511 seems to function as a positive regulator of TLR4. In conclusion, we have identified miR-511 as a novel potent modulator of human immune response. In addition, our data highlight that miRNA influence on gene expression is dependent on the cellular environment.
authors.affiliation: Molecular Pathology, Faculty of Medicine, University of Tartu, Tartu 50411, Estonia.
authors.forename: Liina
authors.initials: L
authors.lastname: Tserel
authors.forename: Toomas
authors.initials: T
authors.lastname: Runnel
authors.forename: Kai
authors.initials: K
authors.lastname: Kisand
authors.forename: Maire
authors.initials: M
authors.lastname: Pihlap
authors.forename: Lairi
authors.initials: L
authors.lastname: Bakhoff
authors.forename: Raivo
authors.initials: R
authors.lastname: Kolde
authors.forename: Hedi
authors.initials: H
authors.lastname: Peterson
authors.forename: Jaak
authors.initials: J
authors.lastname: Vilo
authors.forename: Pärt
authors.initials: P
authors.lastname: Peterson
authors.forename: Ana
authors.initials: A
authors.lastname: Rebane
mesh_terms: D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D018122:B7-1 Antigen; D015815:Cell Adhesion Molecules; D053487:DEAD-box RNA Helicases; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D035683:MicroRNAs; D011956:Receptors, Cell Surface; D043244:Ribonuclease III; D051197:Toll-Like Receptor 4; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C495345:TLR4 protein, human; C408087:DICER1 protein, human