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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...

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Autores principales: Vlacil, Ann-Kathrin, Vollmeister, Evelyn, Bertrams, Wilhelm, Schoesser, Florian, Oberoi, Raghav, Schuett, Jutta, Schuett, Harald, Huehn, Sonja, Bedenbender, Katrin, Schmeck, Bernd T., Schieffer, Bernhard, Grote, Karsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192443/
https://www.ncbi.nlm.nih.gov/pubmed/32353008
http://dx.doi.org/10.1371/journal.pone.0228764
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author Vlacil, Ann-Kathrin
Vollmeister, Evelyn
Bertrams, Wilhelm
Schoesser, Florian
Oberoi, Raghav
Schuett, Jutta
Schuett, Harald
Huehn, Sonja
Bedenbender, Katrin
Schmeck, Bernd T.
Schieffer, Bernhard
Grote, Karsten
author_facet Vlacil, Ann-Kathrin
Vollmeister, Evelyn
Bertrams, Wilhelm
Schoesser, Florian
Oberoi, Raghav
Schuett, Jutta
Schuett, Harald
Huehn, Sonja
Bedenbender, Katrin
Schmeck, Bernd T.
Schieffer, Bernhard
Grote, Karsten
author_sort Vlacil, Ann-Kathrin
collection PubMed
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.
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spelling pubmed-71924432020-05-11 Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells Vlacil, Ann-Kathrin Vollmeister, Evelyn Bertrams, Wilhelm Schoesser, Florian Oberoi, Raghav Schuett, Jutta Schuett, Harald Huehn, Sonja Bedenbender, Katrin Schmeck, Bernd T. Schieffer, Bernhard Grote, Karsten PLoS One Research Article 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. Public Library of Science 2020-04-30 /pmc/articles/PMC7192443/ /pubmed/32353008 http://dx.doi.org/10.1371/journal.pone.0228764 Text en © 2020 Vlacil et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Vlacil, Ann-Kathrin
Vollmeister, Evelyn
Bertrams, Wilhelm
Schoesser, Florian
Oberoi, Raghav
Schuett, Jutta
Schuett, Harald
Huehn, Sonja
Bedenbender, Katrin
Schmeck, Bernd T.
Schieffer, Bernhard
Grote, Karsten
Identification of microRNAs involved in NOD-dependent induction of pro-inflammatory genes in pulmonary endothelial cells
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192443/
https://www.ncbi.nlm.nih.gov/pubmed/32353008
http://dx.doi.org/10.1371/journal.pone.0228764
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