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HDAC6/aggresome processing pathway importance for inflammasome formation is context dependent

The inflammasome is a large multiprotein complex that assembles in the cell cytoplasm in response to stress or pathogenic infection. Its primary function is to defend the cell and promote the secretion of pro-inflammatory cytokines, including IL-1β and IL-18. It was shown that in immortalized bone m...

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Autores principales: Wang, Longlong, Unterreiner, Adeline, Kapetanovic, Ronan, Aslani, Selma, Xiong, Yuan, Donovan, Katherine A., Farady, Christopher J., Fischer, Eric S., Bornancin, Frédéric, Matthias, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461986/
https://www.ncbi.nlm.nih.gov/pubmed/37645730
http://dx.doi.org/10.1101/2023.08.15.553363
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author Wang, Longlong
Unterreiner, Adeline
Kapetanovic, Ronan
Aslani, Selma
Xiong, Yuan
Donovan, Katherine A.
Farady, Christopher J.
Fischer, Eric S.
Bornancin, Frédéric
Matthias, Patrick
author_facet Wang, Longlong
Unterreiner, Adeline
Kapetanovic, Ronan
Aslani, Selma
Xiong, Yuan
Donovan, Katherine A.
Farady, Christopher J.
Fischer, Eric S.
Bornancin, Frédéric
Matthias, Patrick
author_sort Wang, Longlong
collection PubMed
description The inflammasome is a large multiprotein complex that assembles in the cell cytoplasm in response to stress or pathogenic infection. Its primary function is to defend the cell and promote the secretion of pro-inflammatory cytokines, including IL-1β and IL-18. It was shown that in immortalized bone marrow derived macrophages (iBMDMs) inflammasome assembly is dependent on the deacetylase HDAC6 and the aggresome processing pathway (APP), a cellular pathway involved in the disposal of misfolded proteins. Here we used primary BMDMs from mice in which HDAC6 is ablated or impaired and found that inflammasome activation was largely normal. We also used human peripheral blood mononuclear cells and monocytes cell lines expressing a synthetic protein blocking HDAC6-ubiquitin interaction and impairing the APP and found that inflammasome activation was moderately affected. Finally, we used a novel HDAC6 degrader and showed that inflammasome activation was partially impaired in human macrophage cell lines with depleted HDAC6. Our results therefore show that HDAC6 importance in inflammasome activation is context dependent.
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spelling pubmed-104619862023-08-29 HDAC6/aggresome processing pathway importance for inflammasome formation is context dependent Wang, Longlong Unterreiner, Adeline Kapetanovic, Ronan Aslani, Selma Xiong, Yuan Donovan, Katherine A. Farady, Christopher J. Fischer, Eric S. Bornancin, Frédéric Matthias, Patrick bioRxiv Article The inflammasome is a large multiprotein complex that assembles in the cell cytoplasm in response to stress or pathogenic infection. Its primary function is to defend the cell and promote the secretion of pro-inflammatory cytokines, including IL-1β and IL-18. It was shown that in immortalized bone marrow derived macrophages (iBMDMs) inflammasome assembly is dependent on the deacetylase HDAC6 and the aggresome processing pathway (APP), a cellular pathway involved in the disposal of misfolded proteins. Here we used primary BMDMs from mice in which HDAC6 is ablated or impaired and found that inflammasome activation was largely normal. We also used human peripheral blood mononuclear cells and monocytes cell lines expressing a synthetic protein blocking HDAC6-ubiquitin interaction and impairing the APP and found that inflammasome activation was moderately affected. Finally, we used a novel HDAC6 degrader and showed that inflammasome activation was partially impaired in human macrophage cell lines with depleted HDAC6. Our results therefore show that HDAC6 importance in inflammasome activation is context dependent. Cold Spring Harbor Laboratory 2023-08-15 /pmc/articles/PMC10461986/ /pubmed/37645730 http://dx.doi.org/10.1101/2023.08.15.553363 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Wang, Longlong
Unterreiner, Adeline
Kapetanovic, Ronan
Aslani, Selma
Xiong, Yuan
Donovan, Katherine A.
Farady, Christopher J.
Fischer, Eric S.
Bornancin, Frédéric
Matthias, Patrick
HDAC6/aggresome processing pathway importance for inflammasome formation is context dependent
title HDAC6/aggresome processing pathway importance for inflammasome formation is context dependent
title_full HDAC6/aggresome processing pathway importance for inflammasome formation is context dependent
title_fullStr HDAC6/aggresome processing pathway importance for inflammasome formation is context dependent
title_full_unstemmed HDAC6/aggresome processing pathway importance for inflammasome formation is context dependent
title_short HDAC6/aggresome processing pathway importance for inflammasome formation is context dependent
title_sort hdac6/aggresome processing pathway importance for inflammasome formation is context dependent
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461986/
https://www.ncbi.nlm.nih.gov/pubmed/37645730
http://dx.doi.org/10.1101/2023.08.15.553363
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