MicroRNA expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal miR-511 as putative positive regulator of Toll-like receptor 4.
J Biol Chem
; 286(30): 26487-95, 2011 Jul 29.
Article
en En
| MEDLINE
| ID: mdl-21646346
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, â¼50 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
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Monocitos
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Regulación de la Expresión Génica
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MicroARNs
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Receptor Toll-Like 4
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Macrófagos
Idioma:
En
Año:
2011
Tipo del documento:
Article