Activation of the mTOR signaling pathway is required for asthma onset

Abstract 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 ce...

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Autores principales:	Yanli Zhang, Ying Jing, Junying Qiao, Bin Luan, Xiufang Wang, Li Wang, Zhe Song
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8aed2d0d3ffb4dfcbd71494a8323f1d3
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spelling	oai:doaj.org-article:8aed2d0d3ffb4dfcbd71494a8323f1d32021-12-02T12:32:40ZActivation of the mTOR signaling pathway is required for asthma onset10.1038/s41598-017-04826-y2045-2322https://doaj.org/article/8aed2d0d3ffb4dfcbd71494a8323f1d32017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04826-yhttps://doaj.org/toc/2045-2322Abstract 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.Yanli ZhangYing JingJunying QiaoBin LuanXiufang WangLi WangZhe SongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yanli Zhang Ying Jing Junying Qiao Bin Luan Xiufang Wang Li Wang Zhe Song Activation of the mTOR signaling pathway is required for asthma onset
description	Abstract 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	article
author	Yanli Zhang Ying Jing Junying Qiao Bin Luan Xiufang Wang Li Wang Zhe Song
author_facet	Yanli Zhang Ying Jing Junying Qiao Bin Luan Xiufang Wang Li Wang Zhe Song
author_sort	Yanli Zhang
title	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_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_sort	activation of the mtor signaling pathway is required for asthma onset
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8aed2d0d3ffb4dfcbd71494a8323f1d3
work_keys_str_mv	AT yanlizhang activationofthemtorsignalingpathwayisrequiredforasthmaonset AT yingjing activationofthemtorsignalingpathwayisrequiredforasthmaonset AT junyingqiao activationofthemtorsignalingpathwayisrequiredforasthmaonset AT binluan activationofthemtorsignalingpathwayisrequiredforasthmaonset AT xiufangwang activationofthemtorsignalingpathwayisrequiredforasthmaonset AT liwang activationofthemtorsignalingpathwayisrequiredforasthmaonset AT zhesong activationofthemtorsignalingpathwayisrequiredforasthmaonset
_version_	1718393991027752960

Activation of the mTOR signaling pathway is required for asthma onset

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