MicroRNA Expression Profiles of Human Blood Monocyte-derived Dendritic Cells and Macrophages Reveal miR-511 as Putative Positive Regulator of Toll-like Receptor 4
| Autor: | Hedi Peterson, Jaak Vilo, Liina Tserel, Maire Pihlap, Toomas Runnel, Lairi Bakhoff, Raivo Kolde, Kai Kisand, Ana Rebane, Pärt Peterson |
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| Rok vydání: | 2011 |
| Předmět: |
Ribonuclease III
Cellular differentiation CD14 Immunology Lipopolysaccharide Receptors Receptors Cell Surface Biology Biochemistry Monocytes DEAD-box RNA Helicases Humans Lectins C-Type Molecular Biology Regulation of gene expression Gene knockdown Toll-like receptor Gene Expression Profiling Macrophages HEK 293 cells Cell Differentiation Dendritic Cells Cell Biology Cell biology Toll-Like Receptor 4 Gene expression profiling MicroRNAs HEK293 Cells Gene Expression Regulation Gene Knockdown Techniques B7-1 Antigen Cell Adhesion Molecules CD80 |
| Zdroj: | Journal of Biological Chemistry. 286:26487-26495 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m110.213561 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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