Lipids in Health and Disease · 2010 · 134 citations · 20 references
Life SciencesImmunologyPathologyImmunoregulationInflammationInnate ImmunityCytokine BiologyImmune Cell PhysiologyImmune Cell SignalingInflammatory Cell ResponsesInflammatory Cell SignalingInflammatory SignalingAblation MechanismsCell ActivationCeramide SignalingCytokine-mediated T Cell ActivationDihydroceramide MetabolismInterferon Gamma ResponseInterferon-gamma ResponsesInterleukin Regulation
Ceramide kinase (CERK) produces the bioactive lipid ceramide-1-phosphate (C1P) and is a key regulator of ceramide and dihydroceramide levels. It is likely that CERK and C1P play a role in inflammatory processes but the cells involved and the mechanisms used remain to be clarified. In particular, the impact of CERK on T-cell biology has not been studied so far. Here, we used Cerk-/- mice backcrossed with DO11.10/RAG1-/- mice to probe the effect of CERK ablation on T-cell activation. Levels of interleukin (IL)-2, IL-4, IL-5, IL-13, of tumor necrosis factor (TNF)-alpha, and of interferon (INF)-gamma were recorded following ovalbumin challenge in vivo and using ovalbumin-treated splenocytes ex- vivo. Absence of CERK led to a significant decrease in the production of IL-4, thus suggesting that CERK may polarize T cells towards the TH2 cell subtype. However, the importance of CERK to TH2 cell biology will have to be investigated further because in a model of asthma, which is TH2-cell driven, Cerk-/- mice responded like wild-type animals.
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Ceramide Kinase, a Novel Lipid Kinase
Masako Sugiura, Keita Kono, Hong Liu et al. · Journal of Biological Chemistry · 2002 · 297 citations · Full text
Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720
Barbara Zemann, Bernd Kinzel, Mathias Müller et al. · Blood · 2005 · 262 citations · Full text