Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells.
The nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 are mammalian cytosolic pattern recognition receptors sensing bacterial peptidoglycan fragments in order to initiate cytokine expression and pathogen host defense. Since endothelial cells are relevant cells for pathogen...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2020-01-01
|
Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0228764 |
id |
doaj-dc3c623fedb946b2b845447140bb8525 |
---|---|
record_format |
Article |
spelling |
doaj-dc3c623fedb946b2b845447140bb85252021-03-03T21:38:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01154e022876410.1371/journal.pone.0228764Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells.Ann-Kathrin VlacilEvelyn VollmeisterWilhelm BertramsFlorian SchoesserRaghav OberoiJutta SchuettHarald SchuettSonja HuehnKatrin BedenbenderBernd T SchmeckBernhard SchiefferKarsten GroteThe nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 are mammalian cytosolic pattern recognition receptors sensing bacterial peptidoglycan fragments in order to initiate cytokine expression and pathogen host defense. Since endothelial cells are relevant cells for pathogen recognition at the blood/tissue interface, we here analyzed the role of NOD1- and NOD2-dependently expressed microRNAs (miRNAs, miR) for cytokine regulation in murine pulmonary endothelial cells. The induction of inflammatory cytokines in response to NOD1 and NOD2 was confirmed by increased expression of tumour necrosis factor (Tnf)-α and interleukin (Il)-6. MiRNA expression profiling revealed NOD1- and NOD2-dependently regulated miRNA candidates, of which miR-147-3p, miR-200a-3p, and miR-298-5p were subsequently validated in pulmonary endothelial cells isolated from Nod1/2-deficient mice. Analysis of the two down-regulated candidates miR-147-3p and miR-298-5p revealed predicted binding sites in the 3' untranslated region (UTR) of the murine Tnf-α and Il-6 mRNA. Consequently, transfection of endothelial cells with miRNA mimics decreased Tnf-α and Il-6 mRNA levels. Finally, a novel direct interaction of miR-298-5p with the 3' UTR of the Il-6 mRNA was uncovered by luciferase reporter assays. We here identified a mechanism of miRNA-down-regulation by NOD stimulation thereby enabling the induction of inflammatory gene expression in endothelial cells.https://doi.org/10.1371/journal.pone.0228764 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ann-Kathrin Vlacil Evelyn Vollmeister Wilhelm Bertrams Florian Schoesser Raghav Oberoi Jutta Schuett Harald Schuett Sonja Huehn Katrin Bedenbender Bernd T Schmeck Bernhard Schieffer Karsten Grote |
spellingShingle |
Ann-Kathrin Vlacil Evelyn Vollmeister Wilhelm Bertrams Florian Schoesser Raghav Oberoi Jutta Schuett Harald Schuett Sonja Huehn Katrin Bedenbender Bernd T Schmeck Bernhard Schieffer Karsten Grote Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells. PLoS ONE |
author_facet |
Ann-Kathrin Vlacil Evelyn Vollmeister Wilhelm Bertrams Florian Schoesser Raghav Oberoi Jutta Schuett Harald Schuett Sonja Huehn Katrin Bedenbender Bernd T Schmeck Bernhard Schieffer Karsten Grote |
author_sort |
Ann-Kathrin Vlacil |
title |
Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells. |
title_short |
Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells. |
title_full |
Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells. |
title_fullStr |
Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells. |
title_full_unstemmed |
Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells. |
title_sort |
identification of micrornas involved in nod-dependent induction of pro-inflammatory genes in pulmonary endothelial cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
The nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 are mammalian cytosolic pattern recognition receptors sensing bacterial peptidoglycan fragments in order to initiate cytokine expression and pathogen host defense. Since endothelial cells are relevant cells for pathogen recognition at the blood/tissue interface, we here analyzed the role of NOD1- and NOD2-dependently expressed microRNAs (miRNAs, miR) for cytokine regulation in murine pulmonary endothelial cells. The induction of inflammatory cytokines in response to NOD1 and NOD2 was confirmed by increased expression of tumour necrosis factor (Tnf)-α and interleukin (Il)-6. MiRNA expression profiling revealed NOD1- and NOD2-dependently regulated miRNA candidates, of which miR-147-3p, miR-200a-3p, and miR-298-5p were subsequently validated in pulmonary endothelial cells isolated from Nod1/2-deficient mice. Analysis of the two down-regulated candidates miR-147-3p and miR-298-5p revealed predicted binding sites in the 3' untranslated region (UTR) of the murine Tnf-α and Il-6 mRNA. Consequently, transfection of endothelial cells with miRNA mimics decreased Tnf-α and Il-6 mRNA levels. Finally, a novel direct interaction of miR-298-5p with the 3' UTR of the Il-6 mRNA was uncovered by luciferase reporter assays. We here identified a mechanism of miRNA-down-regulation by NOD stimulation thereby enabling the induction of inflammatory gene expression in endothelial cells. |
url |
https://doi.org/10.1371/journal.pone.0228764 |
work_keys_str_mv |
AT annkathrinvlacil identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells AT evelynvollmeister identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells AT wilhelmbertrams identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells AT florianschoesser identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells AT raghavoberoi identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells AT juttaschuett identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells AT haraldschuett identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells AT sonjahuehn identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells AT katrinbedenbender identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells AT berndtschmeck identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells AT bernhardschieffer identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells AT karstengrote identificationofmicrornasinvolvedinnoddependentinductionofproinflammatorygenesinpulmonaryendothelialcells |
_version_ |
1714815942091866112 |