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YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials

Innate anti-inflammatory mechanisms are essential for immune homeostasis and can present opportunities to intervene inflammatory diseases. In this report, we found that YAP isoform 9 (YAP9) is an essential negative regulator of the potent inflammatory stimuli such as TNFα, IL-1β, and LPS. YAP9 const...

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Autores principales: Yang, Fengyuan Mandy, Shen, Liya, Fan, Dengxia Denise, Bai, Yaqin, Li, Bizhou, Lee, Jongdae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420849/
https://www.ncbi.nlm.nih.gov/pubmed/36045678
http://dx.doi.org/10.3389/fimmu.2022.914381
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author Yang, Fengyuan Mandy
Shen, Liya
Fan, Dengxia Denise
Bai, Yaqin
Li, Bizhou
Lee, Jongdae
author_facet Yang, Fengyuan Mandy
Shen, Liya
Fan, Dengxia Denise
Bai, Yaqin
Li, Bizhou
Lee, Jongdae
author_sort Yang, Fengyuan Mandy
collection PubMed
description Innate anti-inflammatory mechanisms are essential for immune homeostasis and can present opportunities to intervene inflammatory diseases. In this report, we found that YAP isoform 9 (YAP9) is an essential negative regulator of the potent inflammatory stimuli such as TNFα, IL-1β, and LPS. YAP9 constitutively interacts with another anti-inflammatory regulator A20 (TNFAIP3) to suppress inflammatory responses, but A20 and YAP can function only in the presence of the other. YAP9 uses a short stretch of amino acids in the proline-rich domain (PRD) and transactivation domain (TAD) suppress the inflammatory signaling while A20 mainly uses the zinc finger domain 7 (ZF7). Cell-penetrating synthetic PRD, TAD, and ZF7 peptides act as YAP9 and A20 mimetics respectively to suppress the proinflammatory responses at the cellular level and in mice. Our data uncover a novel anti-inflammatory axis and anti-inflammatory agents that can be developed to treat acute or chronic conditions where TNFα, IL-1β, or LPS plays a key role in initiating and/or perpetuating inflammation.
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spelling pubmed-94208492022-08-30 YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials Yang, Fengyuan Mandy Shen, Liya Fan, Dengxia Denise Bai, Yaqin Li, Bizhou Lee, Jongdae Front Immunol Immunology Innate anti-inflammatory mechanisms are essential for immune homeostasis and can present opportunities to intervene inflammatory diseases. In this report, we found that YAP isoform 9 (YAP9) is an essential negative regulator of the potent inflammatory stimuli such as TNFα, IL-1β, and LPS. YAP9 constitutively interacts with another anti-inflammatory regulator A20 (TNFAIP3) to suppress inflammatory responses, but A20 and YAP can function only in the presence of the other. YAP9 uses a short stretch of amino acids in the proline-rich domain (PRD) and transactivation domain (TAD) suppress the inflammatory signaling while A20 mainly uses the zinc finger domain 7 (ZF7). Cell-penetrating synthetic PRD, TAD, and ZF7 peptides act as YAP9 and A20 mimetics respectively to suppress the proinflammatory responses at the cellular level and in mice. Our data uncover a novel anti-inflammatory axis and anti-inflammatory agents that can be developed to treat acute or chronic conditions where TNFα, IL-1β, or LPS plays a key role in initiating and/or perpetuating inflammation. Frontiers Media S.A. 2022-08-15 /pmc/articles/PMC9420849/ /pubmed/36045678 http://dx.doi.org/10.3389/fimmu.2022.914381 Text en Copyright © 2022 Yang, Shen, Fan, Bai, Li and Lee https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Yang, Fengyuan Mandy
Shen, Liya
Fan, Dengxia Denise
Bai, Yaqin
Li, Bizhou
Lee, Jongdae
YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials
title YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials
title_full YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials
title_fullStr YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials
title_full_unstemmed YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials
title_short YAP9/A20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials
title_sort yap9/a20 complex suppresses proinflammatory responses and provides novel anti-inflammatory therapeutic potentials
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420849/
https://www.ncbi.nlm.nih.gov/pubmed/36045678
http://dx.doi.org/10.3389/fimmu.2022.914381
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