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MicroRNA expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal miR-511 as putative positive regulator of Toll-like receptor 4


Tserel, L; Runnel, T; Kisand, K; Pihlap, M; Bakhoff, L; Kolde, R; Peterson, H; Vilo, J; Peterson, P; Rebane, A (2011). MicroRNA expression profiles of human blood monocyte-derived dendritic cells and macrophages reveal miR-511 as putative positive regulator of Toll-like receptor 4. Journal of Biological Chemistry, 286(30):26487-26495.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:29 July 2011
Deposited On:05 Mar 2012 16:55
Last Modified:14 Sep 2016 07:27
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in J Biol Chem. 2011 Jul 29;286(30):26487-95. © the American Society for Biochemistry and Molecular Biology.
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1074/jbc.M110.213561
PubMed ID:21646346
Permanent URL: https://doi.org/10.5167/uzh-60307

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