@article{JbeilySuckertGonnertetal.2013,
  author    = {Jbeily, Nayla and Suckert, Iris and Gonnert, Falk A. and Acht, Benedikt and Bockmeyer, Clemens L. and Grossmann, Sascha D. and Blaess, Markus F. and L{\"u}th, Anja and Deigner, Hans-Peter and Bauer, Michael and Claus, Ralf A.},
  title     = {Hyperresponsiveness of mice deficient in plasma-secreted sphingomyelinase reveals its pivotal role in early phase of host response},
  series = {Journal of lipid research},
  volume    = {54},
  journal   = {Journal of lipid research},
  number    = {2},
  publisher = {American Society for Biochemistry and Molecular Biology},
  address   = {Bethesda},
  issn      = {0022-2275},
  doi       = {10.1194/jlr.M031625},
  pages     = {410 -- 424},
  year      = {2013},
  abstract  = {Plasma secretion of acid sphingomyelinase is a hallmark of cellular stress response resulting in the formation of membrane embedded ceramide-enriched lipid rafts and the reorganization of receptor complexes. Consistently, decompartmentalization of ceramide formation from inert sphingomyelin has been associated with signaling events and regulation of the cellular phenotype. Herein, we addressed the question of whether the secretion of acid sphingomyelinase is involved in host response during sepsis. We found an exaggerated clinical course in mice genetically deficient in acid sphingomyelinase characterized by an increased bacterial burden, an increased phagocytotic activity, and a more pronounced cytokine storm. Moreover, on a functional level, leukocyte-endothelial interaction was found diminished in sphingomyelinase-deficient animals corresponding to a distinct leukocytes' phenotype with respect to rolling and sticking as well as expression of cellular surface proteins.(jlr) We conclude that hydrolysis of membrane-embedded sphingomyelin, triggered by circulating sphingomyelinase, plays a pivotal role in the first line of defense against invading microorganisms. This function might be essential during the early phase of infection leading to an adaptive response of remote cells and tissues.-Jbeily, N., I. Suckert, F. A. Gonnert, B. Acht, C. L. Bockmeyer, S. D. Grossmann, M. F. Blaess, A. Lueth, H.-P. Deigner, M. Bauer, and R. A. Claus. Hyperresponsiveness of mice deficient in plasma-secreted sphingomyelinase reveals its pivotal role in early phase of host response. J. Lipid Res. 2013. 54: 410-424.},
  language  = {en}
}
@article{KakkasserySkosyrskiLuethetal.2017,
  author    = {Kakkassery, Vinodh and Skosyrski, S. and L{\"u}th, A. and Kleuser, Burkhard and van der Giet, Maria and Tate, R. and Reinhard, J. and Faissner, Andreas and Joachim, Stephanie Christine and Kociok, N.},
  title     = {Etoposide Upregulates Survival Favoring Sphingosine-1-Phosphate in Etoposide-Resistant Retinoblastoma Cells},
  series = {Pathology \& Oncology Research},
  volume    = {25},
  journal   = {Pathology \& Oncology Research},
  number    = {1},
  publisher = {Springer},
  address   = {Dordrecht},
  issn      = {1219-4956},
  doi       = {10.1007/s12253-017-0360-x},
  pages     = {391 -- 399},
  year      = {2017},
  abstract  = {Improved knowledge of retinoblastoma chemotherapy resistance is needed to raise treatment efficiency. The objective of this study was to test whether etoposide alters glucosyl-ceramide, ceramide, sphingosine, and sphingosine-1-phosphate (sphingosine-1-P) levels in parental retinoblastoma cells (WERI Rb1) or their etoposide-resistant subclones (WERI EtoR). WERI Rb1 and WERI EtoR were incubated with 400 ng/ml etoposide for 24 h. Levels of glucosyl-ceramides, ceramides, sphingosine, sphingosine-1-P were detected by Q-TOF mass spectrometry. Statistical analysis was done by ANOVA followed by Tukey post-hoc test (p < 0.05). The mRNA expression of sphingolipid pathways enzymes in WERI Rb1, WERI EtoR and four human retinoblastoma tissue samples was analyzed by quantitative real-time PCR. Pathways enzymes mRNA expression confirmed similarities of human sphingolipid metabolism in both cell lines and tissue samples, but different relative expression. Significant up-regulation of sphingosine was seen in both cell lines (p < 0.001). Only sphingosine-1-P up-regulation was significantly increased in WERI EtoR (p < 0.01), but not in WERI Rb1 (p > 0.2). Both cell lines upregulate pro-apoptotic sphingosine after etoposide incubation, but only WERI EtoR produces additional survival favorable sphingosine-1-P. These data may suggest a role of sphingosine-1-P in retinoblastoma chemotherapy resistance, although this seems not to be the only resistance mechanism.},
  language  = {en}
}
@article{LotinunKivirantaMatsubaraetal.2013,
  author    = {Lotinun, Sutada and Kiviranta, Riku and Matsubara, Takuma and Alzate, Jorge A. and Neff, Lynn and L{\"u}th, Anja and Koskivirta, Ilpo and Kleuser, Burkhard and Vacher, Jean and Vuorio, Eero and Horne, William C. and Baron, Roland},
  title     = {Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation},
  series = {The journal of clinical investigation},
  volume    = {123},
  journal   = {The journal of clinical investigation},
  number    = {2},
  publisher = {American Society for Clinical Investigation},
  address   = {Ann Arbor},
  issn      = {0021-9738},
  doi       = {10.1172/JCI64840},
  pages     = {666 -- 681},
  year      = {2013},
  abstract  = {Cathepsin K (CTSK) is secreted by osteoclasts to degrade collagen and other matrix proteins during bone resorption. Global deletion of Ctsk in mice decreases bone resorption, leading to osteopetrosis, but also increases the bone formation rate (BFR). To understand how Ctsk deletion increases the BFR, we generated osteoclast- and osteoblast-targeted Ctsk knockout mice using floxed Ctsk alleles. Targeted ablation of Ctsk in hematopoietic cells, or specifically in osteoclasts and cells of the monocyte-osteoclast lineage, resulted in increased bone volume and BFR as well as osteoclast and osteoblast numbers. In contrast, targeted deletion of Ctsk in osteoblasts had no effect on bone resorption or BFR, demonstrating that the increased BFR is osteoclast dependent. Deletion of Ctsk in osteoclasts increased their sphingosine kinase 1 (Sphk1) expression. Conditioned media from Ctsk-deficient osteoclasts, which contained elevated levels of sphingosine-l-phosphate (S1P), increased alkaline phosphatase and mineralized nodules in osteoblast cultures. An S1P(1,3) receptor antagonist inhibited these responses. Osteoblasts derived from mice with Ctsk-deficient osteoclasts had an increased RANKL/OPG ratio, providing a positive feedback loop that increased the number of osteoclasts. Our data provide genetic evidence that deletion of CTSK in osteoclasts enhances bone formation in vivo by increasing the generation of osteoclast-derived S1P.},
  language  = {en}
}