Cargando…

Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines

Tissue-resident macrophages play critical roles in controlling homeostasis, tissue repair, and immunity. Inflammatory macrophages can sustain tissue damage and promote the development of fibrosis during infections and sterile tissue injury. The NLRP3 inflammasome and its effector cytokine IL-1β have...

Descripción completa

Detalles Bibliográficos
Autores principales: Köse-Vogel, Nilay, Stengel, Sven, Gardey, Elena, Kirchberger-Tolstik, Tatiana, Reuken, Philipp A., Stallmach, Andreas, Bruns, Tony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016608/
https://www.ncbi.nlm.nih.gov/pubmed/31905600
http://dx.doi.org/10.3390/cells9010079
_version_ 1783497014142566400
author Köse-Vogel, Nilay
Stengel, Sven
Gardey, Elena
Kirchberger-Tolstik, Tatiana
Reuken, Philipp A.
Stallmach, Andreas
Bruns, Tony
author_facet Köse-Vogel, Nilay
Stengel, Sven
Gardey, Elena
Kirchberger-Tolstik, Tatiana
Reuken, Philipp A.
Stallmach, Andreas
Bruns, Tony
author_sort Köse-Vogel, Nilay
collection PubMed
description Tissue-resident macrophages play critical roles in controlling homeostasis, tissue repair, and immunity. Inflammatory macrophages can sustain tissue damage and promote the development of fibrosis during infections and sterile tissue injury. The NLRP3 inflammasome and its effector cytokine IL-1β have been identified as important mediators of fibrosis. Epirubicin, an anthracycline topoisomerase II inhibitor, has been reported to inhibit myeloid inflammatory cytokine production and to promote tissue tolerance following bacterial infection. We investigated the anti-inflammatory properties of epirubicin on the NLRP3 inflammasome and TLR4-mediated inflammation in PMA-primed THP-1 and in primary human peritoneal macrophages (PM). Low-dose epirubicin at non-cytotoxic doses downregulated NLRP3 inflammasome components and reduced the release of cleaved caspase-1, bioactive IL-1β, and TNF-α following NLRP3 activation in a dose-dependent fashion. In addition, epirubicin attenuated inflammatory macrophage responses after TLR4 and TLR2 ligation. These anti-inflammatory effects were not mediated by the induction of autophagy or altered MAPK signaling, but as the result of a global transcriptional suppression of LPS-dependent genes. Epirubicin-treated macrophages displayed reduced acetylation of histone 3 lysine 9 (H3K9ac), suggesting anti-inflammatory epigenetic imprinting as one underlying mechanism.
format Online
Article
Text
id pubmed-7016608
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70166082020-03-04 Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines Köse-Vogel, Nilay Stengel, Sven Gardey, Elena Kirchberger-Tolstik, Tatiana Reuken, Philipp A. Stallmach, Andreas Bruns, Tony Cells Article Tissue-resident macrophages play critical roles in controlling homeostasis, tissue repair, and immunity. Inflammatory macrophages can sustain tissue damage and promote the development of fibrosis during infections and sterile tissue injury. The NLRP3 inflammasome and its effector cytokine IL-1β have been identified as important mediators of fibrosis. Epirubicin, an anthracycline topoisomerase II inhibitor, has been reported to inhibit myeloid inflammatory cytokine production and to promote tissue tolerance following bacterial infection. We investigated the anti-inflammatory properties of epirubicin on the NLRP3 inflammasome and TLR4-mediated inflammation in PMA-primed THP-1 and in primary human peritoneal macrophages (PM). Low-dose epirubicin at non-cytotoxic doses downregulated NLRP3 inflammasome components and reduced the release of cleaved caspase-1, bioactive IL-1β, and TNF-α following NLRP3 activation in a dose-dependent fashion. In addition, epirubicin attenuated inflammatory macrophage responses after TLR4 and TLR2 ligation. These anti-inflammatory effects were not mediated by the induction of autophagy or altered MAPK signaling, but as the result of a global transcriptional suppression of LPS-dependent genes. Epirubicin-treated macrophages displayed reduced acetylation of histone 3 lysine 9 (H3K9ac), suggesting anti-inflammatory epigenetic imprinting as one underlying mechanism. MDPI 2019-12-28 /pmc/articles/PMC7016608/ /pubmed/31905600 http://dx.doi.org/10.3390/cells9010079 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Köse-Vogel, Nilay
Stengel, Sven
Gardey, Elena
Kirchberger-Tolstik, Tatiana
Reuken, Philipp A.
Stallmach, Andreas
Bruns, Tony
Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines
title Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines
title_full Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines
title_fullStr Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines
title_full_unstemmed Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines
title_short Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines
title_sort transcriptional suppression of the nlrp3 inflammasome and cytokine release in primary macrophages by low-dose anthracyclines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016608/
https://www.ncbi.nlm.nih.gov/pubmed/31905600
http://dx.doi.org/10.3390/cells9010079
work_keys_str_mv AT kosevogelnilay transcriptionalsuppressionofthenlrp3inflammasomeandcytokinereleaseinprimarymacrophagesbylowdoseanthracyclines
AT stengelsven transcriptionalsuppressionofthenlrp3inflammasomeandcytokinereleaseinprimarymacrophagesbylowdoseanthracyclines
AT gardeyelena transcriptionalsuppressionofthenlrp3inflammasomeandcytokinereleaseinprimarymacrophagesbylowdoseanthracyclines
AT kirchbergertolstiktatiana transcriptionalsuppressionofthenlrp3inflammasomeandcytokinereleaseinprimarymacrophagesbylowdoseanthracyclines
AT reukenphilippa transcriptionalsuppressionofthenlrp3inflammasomeandcytokinereleaseinprimarymacrophagesbylowdoseanthracyclines
AT stallmachandreas transcriptionalsuppressionofthenlrp3inflammasomeandcytokinereleaseinprimarymacrophagesbylowdoseanthracyclines
AT brunstony transcriptionalsuppressionofthenlrp3inflammasomeandcytokinereleaseinprimarymacrophagesbylowdoseanthracyclines