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The lncRNA Neat1 promotes activation of inflammasomes in macrophages

The inflammasome has an essential function in innate immune, responding to a wide variety of stimuli. Here we show that the lncRNA Neat1 promotes the activation of several inflammasomes. Neat1 associates with the NLRP3, NLRC4, and AIM2 inflammasomes in mouse macrophages to enhance their assembly and...

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Autores principales: Zhang, Pengfei, Cao, Limian, Zhou, Rongbin, Yang, Xiaolu, Wu, Mian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445148/
https://www.ncbi.nlm.nih.gov/pubmed/30940803
http://dx.doi.org/10.1038/s41467-019-09482-6
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author Zhang, Pengfei
Cao, Limian
Zhou, Rongbin
Yang, Xiaolu
Wu, Mian
author_facet Zhang, Pengfei
Cao, Limian
Zhou, Rongbin
Yang, Xiaolu
Wu, Mian
author_sort Zhang, Pengfei
collection PubMed
description The inflammasome has an essential function in innate immune, responding to a wide variety of stimuli. Here we show that the lncRNA Neat1 promotes the activation of several inflammasomes. Neat1 associates with the NLRP3, NLRC4, and AIM2 inflammasomes in mouse macrophages to enhance their assembly and subsequent pro-caspase-1 processing. Neat1 also stabilizes the mature caspase-1 to promote interleukin-1β production and pyroptosis. Upon stimulation with inflammasome-activating signals, Neat1, which normally resides in the paraspeckles, disassociates from these nuclear bodies and translocates to the cytoplasm to modulate inflammasome activation using above mechanism. Neat1 is also up-regulated under hypoxic conditions in a HIF-2α-dependent manner, mediating the effect of hypoxia on inflammasomes. Moreover, in the mouse models of peritonitis and pneumonia, Neat1 deficiency significantly reduces inflammatory responses. These results reveal a previously unrecognized role of lncRNAs in innate immunity, and suggest that Neat1 is a common mediator for inflammasome stimuli.
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spelling pubmed-64451482019-04-03 The lncRNA Neat1 promotes activation of inflammasomes in macrophages Zhang, Pengfei Cao, Limian Zhou, Rongbin Yang, Xiaolu Wu, Mian Nat Commun Article The inflammasome has an essential function in innate immune, responding to a wide variety of stimuli. Here we show that the lncRNA Neat1 promotes the activation of several inflammasomes. Neat1 associates with the NLRP3, NLRC4, and AIM2 inflammasomes in mouse macrophages to enhance their assembly and subsequent pro-caspase-1 processing. Neat1 also stabilizes the mature caspase-1 to promote interleukin-1β production and pyroptosis. Upon stimulation with inflammasome-activating signals, Neat1, which normally resides in the paraspeckles, disassociates from these nuclear bodies and translocates to the cytoplasm to modulate inflammasome activation using above mechanism. Neat1 is also up-regulated under hypoxic conditions in a HIF-2α-dependent manner, mediating the effect of hypoxia on inflammasomes. Moreover, in the mouse models of peritonitis and pneumonia, Neat1 deficiency significantly reduces inflammatory responses. These results reveal a previously unrecognized role of lncRNAs in innate immunity, and suggest that Neat1 is a common mediator for inflammasome stimuli. Nature Publishing Group UK 2019-04-02 /pmc/articles/PMC6445148/ /pubmed/30940803 http://dx.doi.org/10.1038/s41467-019-09482-6 Text en © The Author(s) 2019 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, Pengfei
Cao, Limian
Zhou, Rongbin
Yang, Xiaolu
Wu, Mian
The lncRNA Neat1 promotes activation of inflammasomes in macrophages
title The lncRNA Neat1 promotes activation of inflammasomes in macrophages
title_full The lncRNA Neat1 promotes activation of inflammasomes in macrophages
title_fullStr The lncRNA Neat1 promotes activation of inflammasomes in macrophages
title_full_unstemmed The lncRNA Neat1 promotes activation of inflammasomes in macrophages
title_short The lncRNA Neat1 promotes activation of inflammasomes in macrophages
title_sort lncrna neat1 promotes activation of inflammasomes in macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445148/
https://www.ncbi.nlm.nih.gov/pubmed/30940803
http://dx.doi.org/10.1038/s41467-019-09482-6
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