@article{HenryNeillBeckeretal.2015,
  author    = {Henry, Brian D. and Neill, Daniel R. and Becker, Katrin Anne and Gore, Suzanna and Bricio-Moreno, Laura and Ziobro, Regan and Edwards, Michael J. and Muehlemann, Kathrin and Steinmann, Joerg and Kleuser, Burkhard and Japtok, Lukasz and Luginbuehl, Miriam and Wolfmeier, Heidi and Scherag, Andre and Gulbins, Erich and Kadioglu, Aras and Draeger, Annette and Babiychuk, Eduard B.},
  title     = {Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice},
  series = {Nature biotechnology : the science and business of biotechnology},
  volume    = {33},
  journal   = {Nature biotechnology : the science and business of biotechnology},
  number    = {1},
  publisher = {Nature Publ. Group},
  address   = {New York},
  issn      = {1087-0156},
  doi       = {10.1038/nbt.3037},
  pages     = {81 -- U295},
  year      = {2015},
  abstract  = {Gram-positive bacterial pathogens that secrete cytotoxic pore-forming toxins, such as Staphylococcus aureus and Streptococcus pneumoniae, cause a substantial burden of disease. Inspired by the principles that govern natural toxin-host interactions, we have engineered artificial liposomes that are tailored to effectively compete with host cells for toxin binding. Liposome-bound toxins are unable to lyse mammalian cells in vitro. We use these artificial liposomes as decoy targets to sequester bacterial toxins that are produced during active infection in vivo. Administration of artificial liposomes within 10 h after infection rescues mice from septicemia caused by S. aureus and S. pneumoniae, whereas untreated mice die within 24-33 h. Furthermore, liposomes protect mice against invasive pneumococcal pneumonia. Composed exclusively of naturally occurring lipids, tailored liposomes are not bactericidal and could be used therapeutically either alone or in conjunction with antibiotics to combat bacterial infections and to minimize toxin-induced tissue damage that occurs during bacterial clearance.},
  language  = {en}
}
@article{BrunoCencettiPerticietal.2015,
  author    = {Bruno, Gennaro and Cencetti, Francesca and Pertici, Irene and Japtok, Lukasz and Bernacchioni, Caterina and Donati, Chiara and Bruni, Paola},
  title     = {CTGF/CCN2 exerts profibrotic action in myoblasts via the up-regulation of sphingosine kinase-1/S1P(3) signaling axis: Implications in the action mechanism of TGF beta},
  series = {Biochimica et biophysica acta : Molecular and cell biology of lipids},
  volume    = {1851},
  journal   = {Biochimica et biophysica acta : Molecular and cell biology of lipids},
  number    = {2},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1388-1981},
  doi       = {10.1016/j.bbalip.2014.11.011},
  pages     = {194 -- 202},
  year      = {2015},
  abstract  = {The matricellular protein connective tissue growth factor (CTGF/CCN2) is recognized as key player in the onset of fibrosis in various tissues, including skeletal muscle. In many circumstances, CTGF has been shown to be induced by transforming growth factor beta (TGF beta) and accounting, at least in part, for its biological action. In this study it was verified that in cultured myoblasts CTGF/CCN2 causes their transdifferentiation into myofibroblasts by up-regulating the expression of fibrosis marker proteins alpha-smooth muscle actin and transgelin. Interestingly, it was also found that the profibrotic effect exerted by CTGF/CCN2 was mediated by the sphingosine kinase (SK)-1/S1P(3) signaling axis specifically induced by the treatment with the profibrotic cue. Following CTGF/CCN2-induced up-regulation, S1P(3) became the SIP receptor subtype expressed at the highest degree, at least at mRNA level, and was thus capable of readdressing the sphingosine 1-phosphate signaling towards fibrosis rather than myogenic differentiation. Another interesting finding is that CTGF/CCN2 silencing prevented the TGF beta-dependent up-regulation of SKI/S1P(3) signaling axis and strongly reduced the profibrotic effect exerted by TGF beta, pointing at a crucial role of endogenous CTGF/CCN2 generated following TGF beta challenge in the transmission of at least part of its profibrotic effect These results provide new insights into the molecular mechanism by which CTGF/CCN2 drives its biological action and strengthen the concept that SK1/S1P(3) axis plays a critical role in the onset of fibrotic cell phenotype. (C) 2014 Elsevier B.V. All rights reserved.},
  language  = {en}
}
@article{CarpinteiroBeckerJaptoketal.2015,
  author    = {Carpinteiro, Alexander and Becker, Katrin Anne and Japtok, Lukasz and Hessler, Gabriele and Keitsch, Simone and Pozgajova, Miroslava and Schmid, Kurt W. and Adams, Constantin and M{\"u}ller, Stefan and Kleuser, Burkhard and Edwards, Michael J. and Grassme, Heike and Helfrich, Iris and Gulbins, Erich},
  title     = {Regulation of hematogenous tumor metastasis by acid sphingomyelinase},
  series = {EMBO molecular medicine},
  volume    = {7},
  journal   = {EMBO molecular medicine},
  number    = {6},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {1757-4676},
  pages     = {714 -- 734},
  year      = {2015},
  abstract  = {Metastatic dissemination of cancer cells is the ultimate hallmark of malignancy and accounts for approximately 90\% of human cancer deaths. We investigated the role of acid sphingomyelinase (Asm) in the hematogenous metastasis of melanoma cells. Intravenous injection of B16F10 melanoma cells into wild-type mice resulted in multiple lung metastases, while Asm-deficient mice (Smpd1(-/-) mice) were protected from pulmonary tumor spread. Transplanting wild-type platelets into Asm-deficient mice reinstated tumor metastasis. Likewise, Asm-deficient mice were protected from hematogenous MT/ret melanoma metastasis to the spleen in a mouse model of spontaneous tumor metastasis. Human and mouse melanoma cells triggered activation and release of platelet secretory Asm, in turn leading to ceramide formation, clustering, and activation of 51 integrins on melanoma cells finally leading to adhesion of the tumor cells. Clustering of integrins by applying purified Asm or C-16 ceramide to B16F10 melanoma cells before intravenous injection restored trapping of tumor cells in the lung in Asm-deficient mice. This effect was revertable by arginine-glycine-aspartic acid peptides, which are known inhibitors of integrins, and by antibodies neutralizing 1 integrins. These findings indicate that melanoma cells employ platelet-derived Asm for adhesion and metastasis.},
  language  = {en}
}
@article{JaptokSchmitzFayyazetal.2015,
  author    = {Japtok, Lukasz and Schmitz, Elisabeth I. and Fayyaz, Susann and Kr{\"a}mer, Stephanie and Hsu, Leigh J. and Kleuser, Burkhard},
  title     = {Sphingosine 1-phosphate counteracts insulin signaling in pancreatic beta-cells via the sphingosine 1-phosphate receptor subtype 2},
  series = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology},
  volume    = {29},
  journal   = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology},
  number    = {8},
  publisher = {Federation of American Societies for Experimental Biology},
  address   = {Bethesda},
  issn      = {0892-6638},
  doi       = {10.1096/fj.14-263194},
  pages     = {3357 -- 3369},
  year      = {2015},
  abstract  = {Glucolipotoxic stress has been identified as a key player in the progression of pancreatic beta-cell dysfunction contributing to insulin resistance and the development of type 2 diabetes mellitus (T2D). It has been suggested that bioactive lipid intermediates, formed under lipotoxic conditions, are involved in these processes. Here, we show that sphingosine 1-phosphate (S1P) levels are not only increased in palmitate-stimulated pancreatic beta-cells but also regulate beta-cell homeostasis in a divergent manner. Although S1P possesses a prosurvival effect in beta-cells, an enhanced level of the sphingolipid antagonizes insulin-mediated cell growth and survival via the sphingosine 1-phosphate receptor subtype 2 (S1P(2)) followed by an inhibition of Akt-signaling. In an attempt to investigate the role of the S1P/S1P(2) axis in vivo, the New Zealand obese (NZO) diabetic mouse model, characterized by beta-cell loss under high-fat diet (HFD) conditions, was used. The occurrence of T2D was accompanied by an increase of plasma S1P levels. To examine whether S1P contributes to the morphologic changes of islets via S1P(2), the receptor antagonist JTE-013 was administered. Most interestingly, JTE-013 rescued beta-cell damage clearly indicating an important role of the S1P(2) in beta-cell homeostasis. Therefore, the present study provides a new therapeutic strategy to diminish beta-cell dysfunction and the development of T2D.},
  language  = {en}
}
@article{LaurenzanaCencettiSerratietal.2015,
  author    = {Laurenzana, Anna and Cencetti, Francesca and Serrati, Simona and Bruno, Gennaro and Japtok, Lukasz and Bianchini, Francesca and Torre, Eugenio and Fibbi, Gabriella and Del Rosso, Mario and Bruni, Paola and Donati, Chiara},
  title     = {Endothelial sphingosine kinase/SPNS2 axis is critical for vessel-like formation by human mesoangioblasts},
  series = {Journal of molecular medicine},
  volume    = {93},
  journal   = {Journal of molecular medicine},
  number    = {10},
  publisher = {Springer},
  address   = {New York},
  issn      = {0946-2716},
  doi       = {10.1007/s00109-015-1292-0},
  pages     = {1145 -- 1157},
  year      = {2015},
  abstract  = {The interaction between endothelial cells and pericytes is crucial for the stabilization of newly formed vessels in angiogenesis. The comprehension of the mechanisms regulating peiicyte recruitment might open therapeutical perspectives on vascular-related pathologies. Sphingosine 1phosphate (SIP) is a bioactive sphingolipid that derives from sphingomyelin catabolism and regulates biological functions in cell survival, proliferation, and differentiation. In this study, we aimed to identify the role of SIP axis in the intercellular communication between human mesenchymal progenitor mesoangioblasts (MAB) and endothelial cells (human microvascular endothelial cells (HMVEC)) in the formation of capillary-like structures. We demonstrated that the SIP biosynthetic pathway brought about by sphingosine kinases (SK) SKI and SK2 as well as spinster homolog 2 (SPNS2) transporter in H-MVEC is crucial for MAB migration measured by Boyden chambers and for the formation and stabilization of capillary-like structures in a 3D Matrigel culture. Moreover, the conditioned medium (CM) harvested from HMVEC, where SKI, 5K2, and SPNS2 were down-regulated, exerted a significantly diminished effect on MAB capillary morphogenesis and migration. Notably, we demonstrated that S I Pi and Si p3 receptors were positively involved in CM-induced capillary-like formation and migration, while S I P2 exerted a negative role on CM-induced migratory action of MAB. Finally, SK inhibition as well as MAB SlPi and S1P3 down-regulation impaired HMVEC-MAB cross-talk significantly reducing in vivo angiogenesis evaluated by Matrigel plug assay. These findings individuate novel targets for the employment of MAB in vascular-related pathologic conditions.},
  language  = {en}
}
@article{MichelsJaptokAlisjahbanaetal.2015,
  author    = {Michels, Meta and Japtok, Lukasz and Alisjahbana, Bachti and Wisaksana, Rudi and Sumardi, Uun and Puspita, Mita and Kleuser, Burkhard and de Mast, Quirijn and van der Ven, Andre J. A. M.},
  title     = {Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage},
  series = {Journal of infection},
  volume    = {71},
  journal   = {Journal of infection},
  number    = {4},
  publisher = {Elsevier},
  address   = {London},
  issn      = {0163-4453},
  doi       = {10.1016/j.jinf.2015.06.014},
  pages     = {480 -- 487},
  year      = {2015},
  abstract  = {Background: A transient endothelial hyperpermeability is a hallmark of severe dengue infections. Sphingosine-1-phosphate (S1P) maintains vascular integrity and protects against plasma leakage. We related plasma S1P levels to dengue-induced plasma leakage and studied mechanisms that may underlie the decrease in S1P levels in dengue. Methods: We determined circulating levels of S1P in 44 Indonesian adults with acute dengue and related levels to plasma leakage, as determined by daily ultrasonography, and to levels of its chaperone apolipoprotein M, other lipoproteins and platelets. Results: Plasma S1P levels were decreased during dengue and patients with plasma leakage had lower median levels compared to those without (638 vs. 745 nM; p < 0.01). ApoM and other lipoprotein levels were also decreased during dengue, but did not correlate to S1P levels. Platelet counts correlated positively with S1P levels, but S1P levels were not higher in frozen-thawed platelet rich plasma, arguing against platelets as an important cellular source of S1P in dengue. Conclusions: Decreased plasma S1P levels during dengue are associated with plasma leakage. We speculate that decreased levels of ApoM underlies the lower S1P levels. Modulation of S1P levels and its receptors may be a novel therapeutic intervention to prevent plasma leakage in dengue. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.},
  language  = {en}
}