PMID- 21646346 OWN - NLM STAT- MEDLINE DCOM- 20110928 LR - 20211020 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 286 IP - 30 DP - 2011 Jul 29 TI - MicroRNA expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal miR-511 as putative positive regulator of Toll-like receptor 4. PG - 26487-95 LID - 10.1074/jbc.M110.213561 [doi] AB - 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, approximately 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. FAU - Tserel, Liina AU - Tserel L AD - Molecular Pathology, Faculty of Medicine, University of Tartu, Tartu 50411, Estonia. FAU - Runnel, Toomas AU - Runnel T FAU - Kisand, Kai AU - Kisand K FAU - Pihlap, Maire AU - Pihlap M FAU - Bakhoff, Lairi AU - Bakhoff L FAU - Kolde, Raivo AU - Kolde R FAU - Peterson, Hedi AU - Peterson H FAU - Vilo, Jaak AU - Vilo J FAU - Peterson, Part AU - Peterson P FAU - Rebane, Ana AU - Rebane A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110606 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (B7-1 Antigen) RN - 0 (Cell Adhesion Molecules) RN - 0 (DC-specific ICAM-3 grabbing nonintegrin) RN - 0 (Lectins, C-Type) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (MicroRNAs) RN - 0 (Receptors, Cell Surface) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - EC 3.1.26.3 (DICER1 protein, human) RN - EC 3.1.26.3 (Ribonuclease III) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) SB - IM MH - B7-1 Antigen/genetics/immunology/metabolism MH - Cell Adhesion Molecules/genetics/immunology/metabolism MH - Cell Differentiation/physiology MH - DEAD-box RNA Helicases/genetics/immunology/metabolism MH - Dendritic Cells/cytology/immunology/*metabolism MH - Gene Expression Profiling MH - Gene Expression Regulation/*physiology MH - Gene Knockdown Techniques MH - HEK293 Cells MH - Humans MH - Lectins, C-Type/genetics/immunology/metabolism MH - Lipopolysaccharide Receptors/genetics/immunology/metabolism MH - Macrophages/cytology/immunology/*metabolism MH - MicroRNAs/*biosynthesis/genetics/immunology/metabolism MH - Monocytes/cytology/immunology/*metabolism MH - Receptors, Cell Surface/genetics/immunology/metabolism MH - Ribonuclease III/genetics/immunology/metabolism MH - Toll-Like Receptor 4/*biosynthesis/genetics/immunology PMC - PMC3143613 EDAT- 2011/06/08 06:00 MHDA- 2011/09/29 06:00 PMCR- 2012/07/29 CRDT- 2011/06/08 06:00 PHST- 2011/06/08 06:00 [entrez] PHST- 2011/06/08 06:00 [pubmed] PHST- 2011/09/29 06:00 [medline] PHST- 2012/07/29 00:00 [pmc-release] AID - S0021-9258(19)48470-6 [pii] AID - M110.213561 [pii] AID - 10.1074/jbc.M110.213561 [doi] PST - ppublish SO - J Biol Chem. 2011 Jul 29;286(30):26487-95. doi: 10.1074/jbc.M110.213561. Epub 2011 Jun 6.