| http://purl.uniprot.org/citations/36361636 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36361636 | http://www.w3.org/2000/01/rdf-schema#comment | "Sphingosine kinases type 1 and 2 (SphK1/2) are required for the production of the immune modulator sphingosine 1-phosphate (S1P). SphK1 deficient mice (SphK1-/-) revealed 50% reduced S1P in plasma, while SphK2-/- mice demonstrated 2-3 times increased S1P levels in plasma. Since plasma S1P is a potent inducer of vascular endothelial cell (VEC) barrier stability, we hypothesized that higher and lower levels of S1P in SphK2-/- and SphK1-/- mice, respectively, compared to wild type (wt) mice should translate into decreased and increased severity of induced systemic inflammation due to improved or damaged VEC barrier maintenance. To our surprise, both SphK1-/- and SphK2-/- mice showed improved survival rate and earlier recovery from inflammation-induced weight loss compared to wt mice. While no difference was observed in VEC barrier stability by monitoring Evans blue leakage into peripheral tissues, SphK1-/- mice demonstrated a distinct delay and SphK2-/- mice an improved resolution of early pro-inflammatory cytokine release in plasma. Ex vivo cell culture experiments demonstrated that bone marrow-derived dendritic cells (BMDC) generated from SphK1-/- and SphK2-/- mice responded with decreased interferon-γ (IFN-γ) production upon stimulation with lipopolysaccharides (LPS) compared to wt BMDC, while activation-induced cytokine expression of lymphocytes and macrophages was not majorly altered. Ex vivo stimulation of macrophages with IFN-γ resulted in increased cytokine release. These results suggest that SphK1/2 are involved in production and secretion of IFN-γ by DC. DC-derived IFN-γ subsequently stimulates the production and secretion of a large panel of inflammatory cytokines by macrophages, which belong to the main cytokine-releasing cells of the early innate immune response. Inhibitors of SphK1/2 may therefore be attractive targets to dampen the early cytokine response of macrophages as part of the innate immune response."xsd:string |
| http://purl.uniprot.org/citations/36361636 | http://purl.org/dc/terms/identifier | "doi:10.3390/ijms232112848"xsd:string |
| http://purl.uniprot.org/citations/36361636 | http://purl.uniprot.org/core/author | "Graler M.H."xsd:string |
| http://purl.uniprot.org/citations/36361636 | http://purl.uniprot.org/core/author | "Reimann C.M."xsd:string |
| http://purl.uniprot.org/citations/36361636 | http://purl.uniprot.org/core/author | "Thuy A.V."xsd:string |
| http://purl.uniprot.org/citations/36361636 | http://purl.uniprot.org/core/author | "Ziegler A.C."xsd:string |
| http://purl.uniprot.org/citations/36361636 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/36361636 | http://purl.uniprot.org/core/name | "Int J Mol Sci"xsd:string |
| http://purl.uniprot.org/citations/36361636 | http://purl.uniprot.org/core/pages | "12848"xsd:string |
| http://purl.uniprot.org/citations/36361636 | http://purl.uniprot.org/core/title | "The Impact of Sphingosine Kinases on Inflammation-Induced Cytokine Release and Vascular Endothelial Barrier Integrity."xsd:string |
| http://purl.uniprot.org/citations/36361636 | http://purl.uniprot.org/core/volume | "23"xsd:string |
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