Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes

Abstract Sirt1, a key regulator of metabolism and longevity, has recently been implicated in the regulation of allergic reactions, although the underlying mechanism remains unclear. Here we show that Sirt1 negatively regulates FcεRI-stimulated mast cell activation and anaphylaxis through two mutuall...

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Autores principales:	Xian Li, Youn Ju Lee, Fansi Jin, Young Na Park, Yifeng Deng, Youra Kang, Ju Hye Yang, Jae-Hoon Chang, Dong-Young Kim, Jung-Ae Kim, Young-Chae Chang, Hyun-Jeong Ko, Cheorl-Ho Kim, Makoto Murakami, Hyeun Wook Chang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe97cadf8a3945a097993ecc828d856a
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spelling	oai:doaj.org-article:fe97cadf8a3945a097993ecc828d856a2021-12-02T12:30:53ZSirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes10.1038/s41598-017-06835-32045-2322https://doaj.org/article/fe97cadf8a3945a097993ecc828d856a2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06835-3https://doaj.org/toc/2045-2322Abstract Sirt1, a key regulator of metabolism and longevity, has recently been implicated in the regulation of allergic reactions, although the underlying mechanism remains unclear. Here we show that Sirt1 negatively regulates FcεRI-stimulated mast cell activation and anaphylaxis through two mutually regulated pathways involving AMP-activated protein kinase (AMPK) and protein tyrosine phosphatase 1B (PTP1B). Mast cell-specific knockout of Sirt1 dampened AMPK-dependent suppression of FcεRI signaling, thereby augmenting mast cell activation both in vitro and in vivo. Sirt1 inhibition of FcεRI signaling also involved an alternative component, PTP1B, which attenuated the inhibitory AMPK pathway and conversely enhanced the stimulatory Syk pathway, uncovering a novel role of this phosphatase. Moreover, a Sirt1 activator resveratrol stimulated the inhibitory AMPK axis, with reciprocal suppression of the stimulatory PTP1B/Syk axis, thus potently inhibiting anaphylaxis. Overall, our results provide a molecular explanation for the beneficial role of Sirt1 in allergy and underscore a potential application of Sirt1 activators as a new class of anti-allergic agents.Xian LiYoun Ju LeeFansi JinYoung Na ParkYifeng DengYoura KangJu Hye YangJae-Hoon ChangDong-Young KimJung-Ae KimYoung-Chae ChangHyun-Jeong KoCheorl-Ho KimMakoto MurakamiHyeun Wook ChangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xian Li Youn Ju Lee Fansi Jin Young Na Park Yifeng Deng Youra Kang Ju Hye Yang Jae-Hoon Chang Dong-Young Kim Jung-Ae Kim Young-Chae Chang Hyun-Jeong Ko Cheorl-Ho Kim Makoto Murakami Hyeun Wook Chang Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes
description	Abstract Sirt1, a key regulator of metabolism and longevity, has recently been implicated in the regulation of allergic reactions, although the underlying mechanism remains unclear. Here we show that Sirt1 negatively regulates FcεRI-stimulated mast cell activation and anaphylaxis through two mutually regulated pathways involving AMP-activated protein kinase (AMPK) and protein tyrosine phosphatase 1B (PTP1B). Mast cell-specific knockout of Sirt1 dampened AMPK-dependent suppression of FcεRI signaling, thereby augmenting mast cell activation both in vitro and in vivo. Sirt1 inhibition of FcεRI signaling also involved an alternative component, PTP1B, which attenuated the inhibitory AMPK pathway and conversely enhanced the stimulatory Syk pathway, uncovering a novel role of this phosphatase. Moreover, a Sirt1 activator resveratrol stimulated the inhibitory AMPK axis, with reciprocal suppression of the stimulatory PTP1B/Syk axis, thus potently inhibiting anaphylaxis. Overall, our results provide a molecular explanation for the beneficial role of Sirt1 in allergy and underscore a potential application of Sirt1 activators as a new class of anti-allergic agents.
format	article
author	Xian Li Youn Ju Lee Fansi Jin Young Na Park Yifeng Deng Youra Kang Ju Hye Yang Jae-Hoon Chang Dong-Young Kim Jung-Ae Kim Young-Chae Chang Hyun-Jeong Ko Cheorl-Ho Kim Makoto Murakami Hyeun Wook Chang
author_facet	Xian Li Youn Ju Lee Fansi Jin Young Na Park Yifeng Deng Youra Kang Ju Hye Yang Jae-Hoon Chang Dong-Young Kim Jung-Ae Kim Young-Chae Chang Hyun-Jeong Ko Cheorl-Ho Kim Makoto Murakami Hyeun Wook Chang
author_sort	Xian Li
title	Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes
title_short	Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes
title_full	Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes
title_fullStr	Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes
title_full_unstemmed	Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes
title_sort	sirt1 negatively regulates fcεri-mediated mast cell activation through ampk- and ptp1b-dependent processes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fe97cadf8a3945a097993ecc828d856a
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Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes

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