Ovalbumin-induced plasma interleukin-4 levels are reduced in ceramide kinase-deficient DO11.10 RAG1-/- mice

被引:13
作者
Niwa, Satoru [1 ]
Urtz, Nicole [1 ]
Baumruker, Thomas [1 ]
Billich, Andreas [1 ]
Bornancin, Frederic [1 ]
机构
[1] Novartis Inst BioMed Res, A-1235 Vienna, Austria
关键词
CYTOSOLIC PHOSPHOLIPASE A(2); LEUKEMIA HL-60 CELLS; 1-PHOSPHATE; SPHINGOMYELIN; GENERATION; INDUCTION; ANTIGEN;
D O I
10.1186/1476-511X-9-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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 T(H)2 cell subtype. However, the importance of CERK to T(H)2 cell biology will have to be investigated further because in a model of asthma, which is T(H)2-cell driven, Cerk(-/-) mice responded like wild-type animals.
引用
收藏
页数:6
相关论文
共 21 条
[1]
Regulation and traffic of ceramide 1-phosphate produced by ceramide kinase - Comparative analysis to glucosylceramide and sphingomyelin [J].
Boath, Alistair ;
Graf, Christine ;
Lidome, Emilie ;
Ullrich, Thomas ;
Nussbaumer, Peter ;
Bornancin, Frederic .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (13) :8517-8526
[2]
DRESSLER KA, 1990, J BIOL CHEM, V265, P14917
[3]
Ceramide 1-phosphate/ceramide, a switch between life and death [J].
Gomez-Munoz, Antonio .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2006, 1758 (12) :2049-2056
[4]
GOMEZMUNOZ A, 1995, MOL PHARMACOL, V47, P883
[5]
Targeting ceramide metabolism with a potent and specific ceramide kinase inhibitor [J].
Graf, Christine ;
Klumpp, Martin ;
Habig, Michael ;
Rovina, Philipp ;
Billich, Andreas ;
Baumruker, Thomas ;
Oberhauser, Berndt ;
Bornancin, Frederic .
MOLECULAR PHARMACOLOGY, 2008, 74 (04) :925-932
[6]
Neutropenia with impaired immune response to Streptococcus pneumoniae in ceramide kinase-deficient mice [J].
Graf, Christine ;
Zemann, Barbara ;
Rovina, Philipp ;
Urtz, Nicole ;
Schanzer, Andrea ;
Reuschel, Roland ;
Mechtcheriakova, Diana ;
Mueller, Matthias ;
Fischer, Evelin ;
Reichel, Claudia ;
Huber, Susanna ;
Dawson, Janet ;
Meingassner, Josef G. ;
Billich, Andreas ;
Niwa, Satoru ;
Badegruber, Rudolf ;
Van Veldhoven, Paul P. ;
Kinzel, Bernd ;
Baumruker, Thomas ;
Bornancin, Frederic .
JOURNAL OF IMMUNOLOGY, 2008, 180 (05) :3457-3466
[7]
Hayashi RJ, 1998, J IMMUNOL, V160, P33
[8]
The formation of ceramide-1-phosphate during neutrophil phagocytosis and its role in liposome fusion [J].
Hinkovska-Galcheva, VT ;
Boxer, LA ;
Mansfield, PJ ;
Harsh, D ;
Blackwood, A ;
Shayman, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (50) :33203-33209
[9]
KOLESNICK RN, 1990, J BIOL CHEM, V265, P18803
[10]
Ceramide 1-Phosphate Is Required for the Translocation of Group IVA Cytosolic Phospholipase A2 and Prostaglandin Synthesis [J].
Lamour, Nadia F. ;
Subramanian, Preeti ;
Wijesinghe, Dayanjan S. ;
Stahelin, Robert V. ;
Bonventre, Joseph V. ;
Chalfant, Charles E. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (39) :26897-26907