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

Ceramide kinase (CERK), together with sphingosine kinases (SPHK) 1 and 2, belongs to the diacyglycerol kinase family of lipid kinases. CERK is the only enzyme known to produce ceramide-1-phosphate (C1P) [1]. However, studies with CERK deficient (Cerk-/-) mice have shown that another route for production of C1P must exist, at least in mammals [2,3]. The best described signaling properties reported for C1P include, on the one hand, a positive effect on cell proliferation and cell survival [4,5] and, on the other hand, the control of cytosolic phospholipase A2 (cPLA2) activity [6-9]. Of note, however, neither knocking down the Cerk gene [3] nor using a CERK inhibitor [10] could recapitulate these findings, which suggests compensation by other C1P pools that do not depend on CERK for their synthesis.The physiological role of CERK and its relevance to disease is only starting to be addressed. Using a gene knockdown strategy Igarashi and coworkers have shown preliminary evidence for a role of CERK in emotional behavior [11]. Based on ex- vivo work with CERK-deficient endothelial cells together with use of the CERK inhibitor NVP-231 [10] our laboratory has recently proposed a role for CERK in the regulation of angiogenesis [12]. CERK may also be relevant to immune cell biology. In fact, neutrophils represent one of the first cell types where CERK/C1P were described [13-15] and subsequently shown to promote phagolysosome formation [16]. More recently, the study of C1P/CERK in mast cells has suggested their function in the degranulation process [17]. Consistently, in a model of passive cutaneous anaphylaxis, Cerk-/- animals were partially protected [3]. However, Cerk-/- responded similarly to control littermates during a model of active cutaneous anaphylaxis [3]. In fact, work in vitro with CERK-deficient primary bone marrow derived mast cells or with the NVP-231 inhibitor failed to clarify a putative role of CERK/C1P in mast cell biology [3,10]. In an antigen-induced arthri