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Article

Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction

1
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany
2
Project Group Translational Medicine and Pharmacology TMP, Fraunhofer Institute for Molecular Biology and Applied Ecology, 60596 Frankfurt, Germany
3
German Cancer Consortium (DKTK), Partner Site Frankfurt, 60590 Frankfurt, Germany
4
Frankfurt Cancer Institute, Goethe-University Frankfurt, 60596 Frankfurt, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4733; https://doi.org/10.3390/ijms21134733
Received: 9 June 2020 / Revised: 26 June 2020 / Accepted: 30 June 2020 / Published: 2 July 2020
(This article belongs to the Special Issue Inflammasome)
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. View Full-Text
Keywords: Macrophage; sphingosine-1-phosphate; NLRP3 inflammasomes; inflammation; IL-1β; renal cell carcinoma; psoriasis Macrophage; sphingosine-1-phosphate; NLRP3 inflammasomes; inflammation; IL-1β; renal cell carcinoma; psoriasis
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MDPI and ACS Style

Syed, S.N.; Weigert, A.; Brüne, B. Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction. Int. J. Mol. Sci. 2020, 21, 4733. https://doi.org/10.3390/ijms21134733

AMA Style

Syed SN, Weigert A, Brüne B. Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction. International Journal of Molecular Sciences. 2020; 21(13):4733. https://doi.org/10.3390/ijms21134733

Chicago/Turabian Style

Syed, Shahzad N., Andreas Weigert, and Bernhard Brüne. 2020. "Sphingosine Kinases are Involved in Macrophage NLRP3 Inflammasome Transcriptional Induction" International Journal of Molecular Sciences 21, no. 13: 4733. https://doi.org/10.3390/ijms21134733

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