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Transcriptional regulation of the IL-13Rα2 gene in human lung fibroblasts
Interleukin (IL)−13 is a type 2 cytokine with important roles in allergic diseases, asthma, and tissue fibrosis. Its receptor (R) α1 is primarily responsible for the biological actions of this cytokine, while Rα2 possesses a decoy function which can block IL-13 signaling. Although the expression of...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978327/ https://www.ncbi.nlm.nih.gov/pubmed/31974428 http://dx.doi.org/10.1038/s41598-020-57972-1 |
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author | Penke, Loka R. Ouchi, Hideyasu Speth, Jennifer M. Lugogo, Njira Huang, Yvonne J. Huang, Steven K. Peters-Golden, Marc |
author_facet | Penke, Loka R. Ouchi, Hideyasu Speth, Jennifer M. Lugogo, Njira Huang, Yvonne J. Huang, Steven K. Peters-Golden, Marc |
author_sort | Penke, Loka R. |
collection | PubMed |
description | Interleukin (IL)−13 is a type 2 cytokine with important roles in allergic diseases, asthma, and tissue fibrosis. Its receptor (R) α1 is primarily responsible for the biological actions of this cytokine, while Rα2 possesses a decoy function which can block IL-13 signaling. Although the expression of Rα2 is known to be subject to modulation, information about its transcriptional regulation is limited. In this study, we sought to expand the understanding of transcriptional control of Rα2 in lung fibroblasts. We confirmed previous reports that IL-13 elicited modest induction of Rα2 in normal adult human lung fibroblasts, but found that prostaglandin E(2) (PGE(2)) and fibroblast growth factor 2 (FGF-2) –mediators known to influence fibroblast activation in tissue fibrosis but not previously investigated in this regard – led to a much greater magnitude of Rα2 induction. Although both PGE(2) (via protein kinase A) and FGF-2 (via protein kinase B, also known as AKT) depended on activation of cAMP-responsive element-binding protein (CREB) for induction of Rα2 expression, they nevertheless demonstrated synergy in doing so, likely attributable to their differential utilization of distinct transcriptional start sites on the Rα2 promoter. Our data identify CREB activation via PGE(2) and FGF-2 as a previously unrecognized molecular controller of Rα2 gene induction and provide potential new insights into strategies for therapeutic manipulation of this endogenous brake on IL-13 signaling. |
format | Online Article Text |
id | pubmed-6978327 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69783272020-01-30 Transcriptional regulation of the IL-13Rα2 gene in human lung fibroblasts Penke, Loka R. Ouchi, Hideyasu Speth, Jennifer M. Lugogo, Njira Huang, Yvonne J. Huang, Steven K. Peters-Golden, Marc Sci Rep Article Interleukin (IL)−13 is a type 2 cytokine with important roles in allergic diseases, asthma, and tissue fibrosis. Its receptor (R) α1 is primarily responsible for the biological actions of this cytokine, while Rα2 possesses a decoy function which can block IL-13 signaling. Although the expression of Rα2 is known to be subject to modulation, information about its transcriptional regulation is limited. In this study, we sought to expand the understanding of transcriptional control of Rα2 in lung fibroblasts. We confirmed previous reports that IL-13 elicited modest induction of Rα2 in normal adult human lung fibroblasts, but found that prostaglandin E(2) (PGE(2)) and fibroblast growth factor 2 (FGF-2) –mediators known to influence fibroblast activation in tissue fibrosis but not previously investigated in this regard – led to a much greater magnitude of Rα2 induction. Although both PGE(2) (via protein kinase A) and FGF-2 (via protein kinase B, also known as AKT) depended on activation of cAMP-responsive element-binding protein (CREB) for induction of Rα2 expression, they nevertheless demonstrated synergy in doing so, likely attributable to their differential utilization of distinct transcriptional start sites on the Rα2 promoter. Our data identify CREB activation via PGE(2) and FGF-2 as a previously unrecognized molecular controller of Rα2 gene induction and provide potential new insights into strategies for therapeutic manipulation of this endogenous brake on IL-13 signaling. Nature Publishing Group UK 2020-01-23 /pmc/articles/PMC6978327/ /pubmed/31974428 http://dx.doi.org/10.1038/s41598-020-57972-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Penke, Loka R. Ouchi, Hideyasu Speth, Jennifer M. Lugogo, Njira Huang, Yvonne J. Huang, Steven K. Peters-Golden, Marc Transcriptional regulation of the IL-13Rα2 gene in human lung fibroblasts |
title | Transcriptional regulation of the IL-13Rα2 gene in human lung fibroblasts |
title_full | Transcriptional regulation of the IL-13Rα2 gene in human lung fibroblasts |
title_fullStr | Transcriptional regulation of the IL-13Rα2 gene in human lung fibroblasts |
title_full_unstemmed | Transcriptional regulation of the IL-13Rα2 gene in human lung fibroblasts |
title_short | Transcriptional regulation of the IL-13Rα2 gene in human lung fibroblasts |
title_sort | transcriptional regulation of the il-13rα2 gene in human lung fibroblasts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978327/ https://www.ncbi.nlm.nih.gov/pubmed/31974428 http://dx.doi.org/10.1038/s41598-020-57972-1 |
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