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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doaj-17b4960fb25042788181ad84c06437cf2020-11-25T03:44:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-01214733473310.3390/ijms21134733Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional InductionShahzad Nawaz Syed0Andreas Weigert1Bernhard Brüne2Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, GermanyInstitute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, GermanyRecent 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.https://www.mdpi.com/1422-0067/21/13/4733Macrophagesphingosine-1-phosphateNLRP3 inflammasomesinflammationIL-1βrenal cell carcinoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shahzad Nawaz Syed Andreas Weigert Bernhard Brüne |
spellingShingle |
Shahzad Nawaz Syed Andreas Weigert Bernhard Brüne Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction International Journal of Molecular Sciences Macrophage sphingosine-1-phosphate NLRP3 inflammasomes inflammation IL-1β renal cell carcinoma |
author_facet |
Shahzad Nawaz Syed Andreas Weigert Bernhard Brüne |
author_sort |
Shahzad Nawaz Syed |
title |
Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction |
title_short |
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_sort |
sphingosine kinases are involved in macrophage nlrp3 inflammasome transcriptional induction |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-07-01 |
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. |
topic |
Macrophage sphingosine-1-phosphate NLRP3 inflammasomes inflammation IL-1β renal cell carcinoma |
url |
https://www.mdpi.com/1422-0067/21/13/4733 |
work_keys_str_mv |
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