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Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction

Recent studies suggested an important contribution of sphingosine-1-phospate (S1P) signaling via its specific receptors (S1PRs) in the production of pro-inflammatory mediators such as Interleukin (IL)-1β in cancer and inflammation. In an inflammation-driven cancer setting, we previously reported tha...

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Autores principales: Syed, Shahzad Nawaz, Weigert, Andreas, Brüne, Bernhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370080/
https://www.ncbi.nlm.nih.gov/pubmed/32630814
http://dx.doi.org/10.3390/ijms21134733
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author Syed, Shahzad Nawaz
Weigert, Andreas
Brüne, Bernhard
author_facet Syed, Shahzad Nawaz
Weigert, Andreas
Brüne, Bernhard
author_sort Syed, Shahzad Nawaz
collection PubMed
description Recent studies suggested an important contribution of sphingosine-1-phospate (S1P) signaling via its specific receptors (S1PRs) in the production of pro-inflammatory mediators such as Interleukin (IL)-1β in cancer and inflammation. In an inflammation-driven cancer setting, we previously reported that myeloid S1PR1 signaling induces IL-1β production by enhancing NLRP3 (NOD-, LRR- and Pyrin Domain-Containing Protein 3) inflammasome activity. However, the autocrine role of S1P and enzymes acting on the S1P rheostat in myeloid cells are unknown. Using human and mouse macrophages with pharmacological or genetic intervention we explored the relative contribution of sphingosine kinases (SPHKs) in NLRP3 inflammasome activity regulation. We noticed redundancy in SPHK1 and SPHK2 activities towards macrophage NLRP3 inflammasome transcriptional induction and IL-1β secretion. However, pharmacological blockade of both kinases in unison completely abrogated NLRP3 inflammasome induction and IL-1β secretion. Interestingly, human and mouse macrophages demonstrate varied responses towards SPHKs inhibition and IL-1β secretion. Clinical datasets of renal cell carcinoma and psoriasis patients showed a positive correlation between enzymes affecting the S1P rheostat with NLRP3 inflammasome components expression, which corroborates our finding. Our data provide a better understanding on the role of SPHKs and de novo synthesized S1P in macrophage NLRP3 inflammasome activation.
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spelling pubmed-73700802020-07-21 Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction Syed, Shahzad Nawaz Weigert, Andreas Brüne, Bernhard Int J Mol Sci Article Recent studies suggested an important contribution of sphingosine-1-phospate (S1P) signaling via its specific receptors (S1PRs) in the production of pro-inflammatory mediators such as Interleukin (IL)-1β in cancer and inflammation. In an inflammation-driven cancer setting, we previously reported that myeloid S1PR1 signaling induces IL-1β production by enhancing NLRP3 (NOD-, LRR- and Pyrin Domain-Containing Protein 3) inflammasome activity. However, the autocrine role of S1P and enzymes acting on the S1P rheostat in myeloid cells are unknown. Using human and mouse macrophages with pharmacological or genetic intervention we explored the relative contribution of sphingosine kinases (SPHKs) in NLRP3 inflammasome activity regulation. We noticed redundancy in SPHK1 and SPHK2 activities towards macrophage NLRP3 inflammasome transcriptional induction and IL-1β secretion. However, pharmacological blockade of both kinases in unison completely abrogated NLRP3 inflammasome induction and IL-1β secretion. Interestingly, human and mouse macrophages demonstrate varied responses towards SPHKs inhibition and IL-1β secretion. Clinical datasets of renal cell carcinoma and psoriasis patients showed a positive correlation between enzymes affecting the S1P rheostat with NLRP3 inflammasome components expression, which corroborates our finding. Our data provide a better understanding on the role of SPHKs and de novo synthesized S1P in macrophage NLRP3 inflammasome activation. MDPI 2020-07-02 /pmc/articles/PMC7370080/ /pubmed/32630814 http://dx.doi.org/10.3390/ijms21134733 Text en © 2020 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
Syed, Shahzad Nawaz
Weigert, Andreas
Brüne, Bernhard
Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction
title Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction
title_full Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction
title_fullStr Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction
title_full_unstemmed Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction
title_short Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction
title_sort sphingosine kinases are involved in macrophage nlrp3 inflammasome transcriptional induction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370080/
https://www.ncbi.nlm.nih.gov/pubmed/32630814
http://dx.doi.org/10.3390/ijms21134733
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