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MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by down-regulation of DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN)

MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by down-regulation of DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN)
MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by down-regulation of DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN)
MicroRNA-155 (miR-155) has been involved in the response to inflammation in macrophages and lymphocytes. Here we show how miR-155 participates in the maturation of human dendritic cells (DC) and modulates pathogen binding by down-regulating DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN), after directly targeting the transcription factor PU.1. During the maturation of DCs, miR-155 increases up to 130-fold, whereas PU.1 protein levels decrease accordingly. We establish that human PU.1 is a direct target for miR-155 and localize the target sequence for miR-155 in the 3'-untranslated region of PU.1. Also, overexpression of miR-155 in the THP1 monocytic cell line decreases PU.1 protein levels and DC-SIGN at both the mRNA and protein levels. We prove a link between the down-regulation of PU.1 and reduced transcriptional activity of the DC-SIGN promoter, which is likely to be the basis for its reduced mRNA expression, after miR-155 overexpression. Finally, we show that, by reducing DC-SIGN in the cellular membrane, miR-155 is involved in regulating pathogen binding as dendritic cells exhibited the lower binding capacity for fungi and HIV protein gp-120 when the levels of miR-155 were higher. Thus, our results suggest a mechanism by which miR-155 regulates proteins involved in the cellular immune response against pathogens that could have clinical implications in the way pathogens enter the human organism.
0021-9258
16334-16342
Martinez-Nunez, Rocio T.
2db66b88-3e6d-4b53-b741-fce5d7b950aa
Louafi, Fethi
75af1544-3c81-4a94-9bd3-50c2c74ad5c4
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Martinez-Nunez, Rocio T.
2db66b88-3e6d-4b53-b741-fce5d7b950aa
Louafi, Fethi
75af1544-3c81-4a94-9bd3-50c2c74ad5c4
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d

Martinez-Nunez, Rocio T., Louafi, Fethi, Friedmann, Peter S. and Sanchez-Elsner, Tilman (2009) MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by down-regulation of DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN). The Journal of Biological Chemistry, 284 (24), 16334-16342. (doi:10.1074/jbc.M109.011601). (PMID:18270516)

Record type: Article

Abstract

MicroRNA-155 (miR-155) has been involved in the response to inflammation in macrophages and lymphocytes. Here we show how miR-155 participates in the maturation of human dendritic cells (DC) and modulates pathogen binding by down-regulating DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN), after directly targeting the transcription factor PU.1. During the maturation of DCs, miR-155 increases up to 130-fold, whereas PU.1 protein levels decrease accordingly. We establish that human PU.1 is a direct target for miR-155 and localize the target sequence for miR-155 in the 3'-untranslated region of PU.1. Also, overexpression of miR-155 in the THP1 monocytic cell line decreases PU.1 protein levels and DC-SIGN at both the mRNA and protein levels. We prove a link between the down-regulation of PU.1 and reduced transcriptional activity of the DC-SIGN promoter, which is likely to be the basis for its reduced mRNA expression, after miR-155 overexpression. Finally, we show that, by reducing DC-SIGN in the cellular membrane, miR-155 is involved in regulating pathogen binding as dendritic cells exhibited the lower binding capacity for fungi and HIV protein gp-120 when the levels of miR-155 were higher. Thus, our results suggest a mechanism by which miR-155 regulates proteins involved in the cellular immune response against pathogens that could have clinical implications in the way pathogens enter the human organism.

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More information

Published date: 22 April 2009
Organisations: Faculty of Medicine, Infection Inflammation & Immunity

Identifiers

Local EPrints ID: 72643
URI: https://eprints.soton.ac.uk/id/eprint/72643
ISSN: 0021-9258
PURE UUID: d75fbdb0-de07-4af9-a223-040116dd1d8e

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Date deposited: 18 Feb 2010
Last modified: 18 Jul 2017 23:53

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Contributors

Author: Rocio T. Martinez-Nunez
Author: Fethi Louafi
Author: Peter S. Friedmann

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