Ovalbumin-induced plasma interleukin-4 levels are reduced in ceramide kinase-deficient DO11.10 RAG1-/- mice.
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.
Niwa
Satoru
S
Novartis Institutes for BioMedical Research, Brunnerstrasse 59, A-1235 Vienna, Austria.
Urtz
Nicole
N
Baumruker
Thomas
T
Billich
Andreas
A
Bornancin
Frédéric
F
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D015971:Gene Expression Regulation, Enzymologic; D018398:Homeodomain Proteins / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000097:blood*; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018398:Homeodomain Proteins; D014409:Tumor Necrosis Factor-alpha; C064658:RAG-1 protein; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase