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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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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. |
format | Online Article Text |
id | pubmed-6261595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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