Cargando…
Activation of the mTOR signaling pathway is required for asthma onset
The mTOR pathway has been implicated in immune functions; however, its role in asthma is not well understood. We found that patients experiencing an asthma attack, when compared with patients in asthma remission, showed significantly elevated serum mTOR pathway activation, increased Th17 cells and I...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495772/ https://www.ncbi.nlm.nih.gov/pubmed/28674387 http://dx.doi.org/10.1038/s41598-017-04826-y |
_version_ | 1783247845371936768 |
---|---|
author | Zhang, Yanli Jing, Ying Qiao, Junying Luan, Bin Wang, Xiufang Wang, Li Song, Zhe |
author_facet | Zhang, Yanli Jing, Ying Qiao, Junying Luan, Bin Wang, Xiufang Wang, Li Song, Zhe |
author_sort | Zhang, Yanli |
collection | PubMed |
description | The mTOR pathway has been implicated in immune functions; however, its role in asthma is not well understood. We found that patients experiencing an asthma attack, when compared with patients in asthma remission, showed significantly elevated serum mTOR pathway activation, increased Th17 cells and IL-4, and decreased Treg cells and IFN-γ. In patients experiencing asthma, mTOR activation was positively correlated with the loss of Th17/Treg and Th1/Th2 balance. The role of mTOR in asthma was further confirmed using an ovalbumin-induced asthmatic mouse model. The mTOR pathway was activated in asthmatic mice, demonstrated by elevated levels of p-PI3K, p-Akt, p-mTOR, and p-p70S6k, and this activation was significantly reduced by treatment with budenoside or mTOR pathway inhibitors. Moreover, mTOR pathway inhibitor treatment reduced asthmatic markers and reversed the Th17/Treg and Th1/Th2 imbalances in asthmatic mice. Finally, different mTOR pathway inhibitor treatments have different inhibitory effects on signaling molecules in asthmatic mice. In summary, mTOR is activated during asthma onset and suppressed during asthma remission, and inhibiting the mTOR pathway in asthmatic mice alleviates asthmatic markers and restores the balances of Th17/Treg and Th1/Th2 cytokines. These data strongly suggest a critical requirement for mTOR pathway activation in asthma onset, suggesting potential targets for asthma treatments. |
format | Online Article Text |
id | pubmed-5495772 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-54957722017-07-07 Activation of the mTOR signaling pathway is required for asthma onset Zhang, Yanli Jing, Ying Qiao, Junying Luan, Bin Wang, Xiufang Wang, Li Song, Zhe Sci Rep Article The mTOR pathway has been implicated in immune functions; however, its role in asthma is not well understood. We found that patients experiencing an asthma attack, when compared with patients in asthma remission, showed significantly elevated serum mTOR pathway activation, increased Th17 cells and IL-4, and decreased Treg cells and IFN-γ. In patients experiencing asthma, mTOR activation was positively correlated with the loss of Th17/Treg and Th1/Th2 balance. The role of mTOR in asthma was further confirmed using an ovalbumin-induced asthmatic mouse model. The mTOR pathway was activated in asthmatic mice, demonstrated by elevated levels of p-PI3K, p-Akt, p-mTOR, and p-p70S6k, and this activation was significantly reduced by treatment with budenoside or mTOR pathway inhibitors. Moreover, mTOR pathway inhibitor treatment reduced asthmatic markers and reversed the Th17/Treg and Th1/Th2 imbalances in asthmatic mice. Finally, different mTOR pathway inhibitor treatments have different inhibitory effects on signaling molecules in asthmatic mice. In summary, mTOR is activated during asthma onset and suppressed during asthma remission, and inhibiting the mTOR pathway in asthmatic mice alleviates asthmatic markers and restores the balances of Th17/Treg and Th1/Th2 cytokines. These data strongly suggest a critical requirement for mTOR pathway activation in asthma onset, suggesting potential targets for asthma treatments. Nature Publishing Group UK 2017-07-03 /pmc/articles/PMC5495772/ /pubmed/28674387 http://dx.doi.org/10.1038/s41598-017-04826-y Text en © The Author(s) 2017 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 Zhang, Yanli Jing, Ying Qiao, Junying Luan, Bin Wang, Xiufang Wang, Li Song, Zhe Activation of the mTOR signaling pathway is required for asthma onset |
title | Activation of the mTOR signaling pathway is required for asthma onset |
title_full | Activation of the mTOR signaling pathway is required for asthma onset |
title_fullStr | Activation of the mTOR signaling pathway is required for asthma onset |
title_full_unstemmed | Activation of the mTOR signaling pathway is required for asthma onset |
title_short | Activation of the mTOR signaling pathway is required for asthma onset |
title_sort | activation of the mtor signaling pathway is required for asthma onset |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495772/ https://www.ncbi.nlm.nih.gov/pubmed/28674387 http://dx.doi.org/10.1038/s41598-017-04826-y |
work_keys_str_mv | AT zhangyanli activationofthemtorsignalingpathwayisrequiredforasthmaonset AT jingying activationofthemtorsignalingpathwayisrequiredforasthmaonset AT qiaojunying activationofthemtorsignalingpathwayisrequiredforasthmaonset AT luanbin activationofthemtorsignalingpathwayisrequiredforasthmaonset AT wangxiufang activationofthemtorsignalingpathwayisrequiredforasthmaonset AT wangli activationofthemtorsignalingpathwayisrequiredforasthmaonset AT songzhe activationofthemtorsignalingpathwayisrequiredforasthmaonset |