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RORα controls inflammatory state of human macrophages

ROR family of nuclear receptor transcription factors forms nodes connecting metabolic and inflammatory signaling pathways. The RORα members of the family have intrinsic transcriptional activity and they are involved in both activation and repression of a wide range of genes. The role of RORα in cont...

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Autores principales: Nejati Moharrami, Neda, Bjørkøy Tande, Erlend, Ryan, Liv, Espevik, Terje, Boyartchuk, Victor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261595/
https://www.ncbi.nlm.nih.gov/pubmed/30485323
http://dx.doi.org/10.1371/journal.pone.0207374
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author Nejati Moharrami, Neda
Bjørkøy Tande, Erlend
Ryan, Liv
Espevik, Terje
Boyartchuk, Victor
author_facet Nejati Moharrami, Neda
Bjørkøy Tande, Erlend
Ryan, Liv
Espevik, Terje
Boyartchuk, Victor
author_sort Nejati Moharrami, Neda
collection PubMed
description ROR family of nuclear receptor transcription factors forms nodes connecting metabolic and inflammatory signaling pathways. The RORα members of the family have intrinsic transcriptional activity and they are involved in both activation and repression of a wide range of genes. The role of RORα in control of inflammation has been extensively studied using animal models but its function in human cells is not as well understood. To address this shortcoming, we analyzed how RORα is shaping the inflammatory state of human macrophages. Using CRISPR-Cas9 system, we deleted RORA in THP-1 human monocytic cell line. In mutant cells we observed a dramatic increase in basal expression of a subset of NF-κB regulated genes, including TNF, IL-1β and IL-6, at both transcriptional and translational levels. Furthermore, RORA-deletion cells produced notable amounts of pro-IL-1β even in the absence of LPS stimulation. Subsequent LPS stimulation induced cleavage of pro-IL-1β to mature form. Our RNAseq analysis further confirmed the key role of RORA in setting the inflammatory state of macrophages and defined the set of differentially regulated genes. Overall, our data provides evidence supporting the anti-inflammatory function of RORα in human macrophages.
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spelling pubmed-62615952018-12-19 RORα controls inflammatory state of human macrophages Nejati Moharrami, Neda Bjørkøy Tande, Erlend Ryan, Liv Espevik, Terje Boyartchuk, Victor PLoS One Research Article ROR family of nuclear receptor transcription factors forms nodes connecting metabolic and inflammatory signaling pathways. The RORα members of the family have intrinsic transcriptional activity and they are involved in both activation and repression of a wide range of genes. The role of RORα in control of inflammation has been extensively studied using animal models but its function in human cells is not as well understood. To address this shortcoming, we analyzed how RORα is shaping the inflammatory state of human macrophages. Using CRISPR-Cas9 system, we deleted RORA in THP-1 human monocytic cell line. In mutant cells we observed a dramatic increase in basal expression of a subset of NF-κB regulated genes, including TNF, IL-1β and IL-6, at both transcriptional and translational levels. Furthermore, RORA-deletion cells produced notable amounts of pro-IL-1β even in the absence of LPS stimulation. Subsequent LPS stimulation induced cleavage of pro-IL-1β to mature form. Our RNAseq analysis further confirmed the key role of RORA in setting the inflammatory state of macrophages and defined the set of differentially regulated genes. Overall, our data provides evidence supporting the anti-inflammatory function of RORα in human macrophages. Public Library of Science 2018-11-28 /pmc/articles/PMC6261595/ /pubmed/30485323 http://dx.doi.org/10.1371/journal.pone.0207374 Text en © 2018 Nejati Moharrami 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
Nejati Moharrami, Neda
Bjørkøy Tande, Erlend
Ryan, Liv
Espevik, Terje
Boyartchuk, Victor
RORα controls inflammatory state of human macrophages
title RORα controls inflammatory state of human macrophages
title_full RORα controls inflammatory state of human macrophages
title_fullStr RORα controls inflammatory state of human macrophages
title_full_unstemmed RORα controls inflammatory state of human macrophages
title_short RORα controls inflammatory state of human macrophages
title_sort rorα controls inflammatory state of human macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261595/
https://www.ncbi.nlm.nih.gov/pubmed/30485323
http://dx.doi.org/10.1371/journal.pone.0207374
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