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m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response
N6-methyladenosine (m6A) is an abundant mRNA modification that affects multiple biological processes, including those involved in the cell stress response and viral infection. YTH domain family 2 (YTHDF2) is an m6A-binding protein that affects the localization and stability of targeted mRNA. RNA-bin...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470741/ https://www.ncbi.nlm.nih.gov/pubmed/30875984 http://dx.doi.org/10.3390/ijms20061323 |
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author | Yu, Ruiqing Li, Qimeng Feng, Zhihui Cai, Luhui Xu, Qiong |
author_facet | Yu, Ruiqing Li, Qimeng Feng, Zhihui Cai, Luhui Xu, Qiong |
author_sort | Yu, Ruiqing |
collection | PubMed |
description | N6-methyladenosine (m6A) is an abundant mRNA modification that affects multiple biological processes, including those involved in the cell stress response and viral infection. YTH domain family 2 (YTHDF2) is an m6A-binding protein that affects the localization and stability of targeted mRNA. RNA-binding proteins (RBPs) can regulate the stability of inflammatory gene mRNA transcripts, thus participating in the regulation of inflammatory processes. As an RBP, the role of YTHDF2 in the LPS-induced inflammatory reaction has not been reported. To elucidate the function of YTHDF2 in the inflammatory response of macrophages, we first detected the expression level of YTHDF2 in RAW 264.7 cells, and found that it was upregulated after LPS stimulation. YTHDF2 knockdown significantly increased the LPS-induced IL-6, TNF-α, IL-1β, and IL-12 expression and the phosphorylation of p65, p38, and ERK1/2 in NF-κB and MAPK signaling. Moreover, the upregulated expression of TNF-α and IL-6 in cells with silenced YTHDF2 expression was downregulated by the NF-κB, p38, and ERK inhibitors. YTHDF2 depletion increased the expression and stability of MAP2K4 and MAP4K4 mRNAs. All of these results suggest that YTHDF2 knockdown increases mRNA expression levels of MAP2K4 and MAP4K4 via stabilizing the mRNA transcripts, which activate MAPK and NF-κB signaling pathways, which promote the expression of proinflammatory cytokines and aggravate the inflammatory response in LPS-stimulated RAW 264.7 cells. |
format | Online Article Text |
id | pubmed-6470741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64707412019-04-26 m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response Yu, Ruiqing Li, Qimeng Feng, Zhihui Cai, Luhui Xu, Qiong Int J Mol Sci Article N6-methyladenosine (m6A) is an abundant mRNA modification that affects multiple biological processes, including those involved in the cell stress response and viral infection. YTH domain family 2 (YTHDF2) is an m6A-binding protein that affects the localization and stability of targeted mRNA. RNA-binding proteins (RBPs) can regulate the stability of inflammatory gene mRNA transcripts, thus participating in the regulation of inflammatory processes. As an RBP, the role of YTHDF2 in the LPS-induced inflammatory reaction has not been reported. To elucidate the function of YTHDF2 in the inflammatory response of macrophages, we first detected the expression level of YTHDF2 in RAW 264.7 cells, and found that it was upregulated after LPS stimulation. YTHDF2 knockdown significantly increased the LPS-induced IL-6, TNF-α, IL-1β, and IL-12 expression and the phosphorylation of p65, p38, and ERK1/2 in NF-κB and MAPK signaling. Moreover, the upregulated expression of TNF-α and IL-6 in cells with silenced YTHDF2 expression was downregulated by the NF-κB, p38, and ERK inhibitors. YTHDF2 depletion increased the expression and stability of MAP2K4 and MAP4K4 mRNAs. All of these results suggest that YTHDF2 knockdown increases mRNA expression levels of MAP2K4 and MAP4K4 via stabilizing the mRNA transcripts, which activate MAPK and NF-κB signaling pathways, which promote the expression of proinflammatory cytokines and aggravate the inflammatory response in LPS-stimulated RAW 264.7 cells. MDPI 2019-03-15 /pmc/articles/PMC6470741/ /pubmed/30875984 http://dx.doi.org/10.3390/ijms20061323 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yu, Ruiqing Li, Qimeng Feng, Zhihui Cai, Luhui Xu, Qiong m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response |
title | m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response |
title_full | m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response |
title_fullStr | m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response |
title_full_unstemmed | m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response |
title_short | m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response |
title_sort | m6a reader ythdf2 regulates lps-induced inflammatory response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470741/ https://www.ncbi.nlm.nih.gov/pubmed/30875984 http://dx.doi.org/10.3390/ijms20061323 |
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