Sphingosine Kinases promote IL-17 expression in human T lymphocytes.
Giusi BarraAlessio LeporeMiriam GagliardiDomenico SommaMaria Rosaria MatarazzoFrancesca CostabileGiuseppe PasqualeAlessio MazzoniCarmela GalloGenoveffa NuzzoFrancesco AnnunziatoAngelo FontanaAntonio LeonardiRaffaele De PalmaPublished in: Scientific reports (2018)
Sphingosine 1-phosphate (S1P) has a role in many cellular processes. S1P is involved in cell growth and apoptosis, regulation of cell trafficking, production of cytokines and chemokines. The kinases SphK1 and SphK2 (SphKs) phosphorilate Sphingosine (Sph) to S1P and several phosphatases revert S1P to sphingosine, thus assuring a balanced pool that can be depleted by a Sphingosine lyase in hexadecenal compounds and aldehydes. There are evidences that SphK1 and 2 may per se control cellular processes. Here, we report that Sph kinases regulate IL-17 expression in human T cells. SphKs inhibition impairs the production of IL-17, while their overexpression up-regulates expression of the cytokine through acetylation of IL-17 promoter. SphKs were up-regulated also in PBMCs of patients affected by IL-17 related diseases. Thus, S1P/S1P kinases axis is a mechanism likely to promote IL-17 expression in human T cells, representing a possible therapeutic target in human inflammatory diseases.
Keyphrases
- endothelial cells
- poor prognosis
- induced pluripotent stem cells
- pluripotent stem cells
- end stage renal disease
- gene expression
- oxidative stress
- long non coding rna
- stem cells
- dna methylation
- ejection fraction
- chronic kidney disease
- cell death
- single cell
- bone marrow
- mesenchymal stem cells
- endoplasmic reticulum stress
- pi k akt
- cell cycle arrest
- drug induced
- signaling pathway