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 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
Verfasserangaben: | Shahzad Nawaz SyedORCiDGND, Andreas WeigertORCiDGND, Bernhard BrüneORCiD |
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URN: | urn:nbn:de:hebis:30:3-554600 |
DOI: | https://doi.org/10.3390/ijms21134733 |
ISSN: | 1422-0067 |
Titel des übergeordneten Werkes (Französisch): | International journal of molecular sciences |
Verlag: | MDPI |
Verlagsort: | Basel |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 02.07.2020 |
Datum der Erstveröffentlichung: | 02.07.2020 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 25.08.2020 |
Freies Schlagwort / Tag: | IL-1β; NLRP3 inflammasomes; inflammation; macrophage; psoriasis; renal cell carcinoma; sphingosine-1-phosphate |
Jahrgang: | 21 |
Ausgabe / Heft: | 13, art. 4733 |
Seitenzahl: | 18 |
Erste Seite: | 1 |
Letzte Seite: | 18 |
Bemerkung: | © 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/). |
HeBIS-PPN: | 469734167 |
Institute: | Medizin |
DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Open-Access-Publikationsfonds: | Medizin |
Lizenz (Deutsch): | Creative Commons - Namensnennung 4.0 |