Refine
Has Fulltext
- no (102) (remove)
Year of publication
Document Type
- Article (102) (remove)
Language
- English (102)
Is part of the Bibliography
- yes (102)
Keywords
- acid sphingomyelinase (9)
- ceramide (9)
- Sphingolipids (7)
- sphingolipids (7)
- Dexamethasone (5)
- Sphingosine 1-phosphate (5)
- acid ceramidase (4)
- Drug delivery systems (3)
- Insulin resistance (3)
- Sphingosine-1-phosphate (3)
- sphingosine (3)
- sphingosine-1-phosphate (3)
- Acid sphingomyelinase (2)
- Biomarker (2)
- Ceramide (2)
- Clinical (2)
- DNA methylation (2)
- Dendritic cells (2)
- Dermal delivery (2)
- Drug delivery (2)
- FTY720 (2)
- Farber disease (2)
- Fluorescence lifetime imaging microscopy (2)
- Gestational diabetes (2)
- Global DNA methylation (2)
- Hepatocytes (2)
- LC-MS/MS (2)
- Metabolomics (2)
- Nanoparticle (2)
- Nanoparticle uptake (2)
- Nanotoxicology (2)
- Palmitate (2)
- Placenta (2)
- Pseudomonas aeruginosa (2)
- Skin nanocarrier (2)
- Skin penetration (2)
- Tandem mass spectrometry (2)
- Ulcerative colitis (2)
- amitriptyline (2)
- cystic fibrosis (2)
- liver metabolism (2)
- lysosomal storage disorders (2)
- measles virus (2)
- platelets (2)
- sphingomyelin (2)
- survival (2)
- (2E)-Hexadecenal (1)
- (2E)-hexadecenal (1)
- (2E)-hexadecenoic acid (1)
- 1-aminodecylidene bis-phosphonic acid (1)
- 1-phosphate (1)
- 3D tissue model (1)
- APOM protein (1)
- Acinetobacter baumannii (1)
- Adipocytes (1)
- Adipose tissue (1)
- Aging (1)
- Akt (1)
- Akt signaling (1)
- Alcohol dependence (1)
- Anxiety (1)
- Apoptosis (1)
- Arsenic speciation (1)
- Arsenic-containing hydrocarbons (1)
- Arsenolipids (1)
- Aryl-hydrocarbon receptor (1)
- Atherosclerosis (1)
- Atopic dermatitis (1)
- Autotaxin (1)
- B cells (1)
- Biocompatibility (1)
- Biocompatibility testing (1)
- Blood platelets (1)
- Broad-spectrum antibiotic therapy (1)
- Brown adipose tissue (1)
- CMS (1)
- CXCR2 (1)
- Caenorhabditis elegans (1)
- Cardiovascular (1)
- Case-control study (1)
- Cellular uptake (1)
- Cellulose acetate phthalate (1)
- Ceramidase inhibitors (1)
- Ceramides (1)
- Chemotherapy resistance (1)
- Citrobacter rodentium (1)
- Coating (1)
- Colitis (1)
- Colon cancer (1)
- Core-multishell nanocarriers (1)
- Cyp2b1 (1)
- DAIH (1)
- DNMT inhibitor (1)
- Delta F508 mutation (1)
- Dendritic core-multishell nanocarriers (1)
- Dengue (1)
- Depression (1)
- Derivatisation (1)
- Derivatization (1)
- Dermal drug delivery (1)
- Diagnostic (1)
- Dichlorofluorescein assay (1)
- Disease (1)
- Dolichol lipids (1)
- Dopamine (1)
- EBI3 (1)
- EDC (1)
- Electron paramagnetic resonance spectroscopy (1)
- Endocrine disruption (1)
- Endothelial cells (1)
- Endothelial nitric oxide synthase (1)
- Energy expenditure (1)
- Enteric polymer (1)
- Epigenetic (1)
- Epigenetics (1)
- Erosion kinetics (1)
- Ethyl cellulose (1)
- Eudragit (R) (1)
- Eudragit (R) RS (1)
- Eudragit L 100 (1)
- FGF21 (1)
- Factor-Xa (1)
- Fetal programming (1)
- Fingolimod (1)
- Fluorescence (1)
- Forster resonance energy transfer (FRET) (1)
- Free radicals (1)
- Gastrointestinal tract (1)
- Gene expression (1)
- Global (1)
- Glp1r(-/-) mice (1)
- Glutathione (1)
- Glycerophospholipids (1)
- HNRNPA1 (1)
- HPLC-ESI-QTOF (1)
- HPMCP (1)
- HaCaT cells (1)
- Hepatic insulin resistance (1)
- Hepatic stellate cells (1)
- High resolution microscopy (1)
- Histone deacetylase inhibitor (1)
- Human (1)
- Hyperglycaemia (1)
- Hypermethylation (1)
- IDH1 (1)
- Imiquimod (1)
- Inflammatory skin disease (1)
- Inhibitory cytokines (1)
- Insulin signaling (1)
- Insulin signalling (1)
- Interleukin-35 (1)
- Ischemia/reperfusion (1)
- Isotope-dilution (1)
- Isotope-dilution analysis (1)
- Jurkat cells (1)
- Keratinocytes (1)
- LPA(3) receptor subtype (1)
- Langerhans cells (1)
- Lipogenesis (1)
- Liquid chromatography-tandem mass spectrometry (1)
- Liver (1)
- Liver fibrosis (1)
- Liver injury (1)
- Lysophosphatidic acid (1)
- Lysophosphatidylcholines (1)
- Mass spectrometry (1)
- Metabolism (1)
- Methylation (1)
- Microbiota (1)
- Microdialysis (1)
- Multi-domain nanoparticles (1)
- Multiple sclerosis (1)
- NZO (1)
- Nanogel (1)
- Nanomaterials (1)
- Nanoparticles (1)
- Neisseria gonorrhoeae (1)
- Nitric oxide (1)
- Obesity (1)
- Ocular delivery (1)
- Oxazolone (1)
- Oxidative stress (1)
- PCaaC38:6 (1)
- PTEN (1)
- Penetration enhancement (1)
- Permeability (1)
- Phosphatidylcholine acyl-alkyl C 32:1 (1)
- Phosphatidylcholines (1)
- Phosphatidylinositols (1)
- Plasma (1)
- Plasmalogens (1)
- Plastic surfaces (1)
- Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] (1)
- Polymeric nanoparticle (1)
- Polymeric nanoparticles (1)
- Polymers (1)
- Pregnancy (1)
- Preterm birth (1)
- Proliferation (1)
- Proline (1)
- Protein restriction (1)
- Psoriasis (1)
- Retinoblastoma (1)
- S1P receptors (1)
- S1P-receptors (1)
- SAHA (1)
- SCID mice (1)
- ST-1071 (1)
- ST-1893 (1)
- ST-1894 (1)
- ST-968 (1)
- Selenium (1)
- Serotonin (1)
- Skeletal muscle cells (1)
- Skin (1)
- Skin absorption (1)
- Skin barrier disruption (1)
- Skin model (1)
- Smooth muscle cells (1)
- Smpd1 (1)
- Sphingomyelin (1)
- Sphingosine (1)
- Sphingosine 1phosphate (1)
- Sphingosine kinase (1)
- Sphingosine kinase-1 (1)
- Sphingosine-1-phosphate lyase (1)
- Srebf1 (1)
- Staphylococcus aureus (1)
- Structure-activity-relationship (1)
- T cell receptor (1)
- T(h)1 (1)
- T(h)17 (1)
- TET (1)
- TGF-beta 1 (1)
- TNF alpha (1)
- TRPC6 (1)
- Thyroid hormone (1)
- Topical treatment (1)
- Transplantation (1)
- Type 2 diabetes (1)
- UDP-glucuronosyltransferase (1)
- Ventilation (1)
- Ventilator-induced lung injury (1)
- Vitamin C (1)
- Xenobesity (1)
- YB-1 (1)
- acid ceramidase inhibitor ceranib-2 (1)
- acute lung injury (1)
- alpha-SMA (1)
- annexins (1)
- anti-inflammatory therapy (1)
- anticancer (1)
- antidepressants (1)
- anxiety-like behavior (1)
- appetite (1)
- autoimmunity (1)
- bacterial toxins (1)
- binding (1)
- birth weight (1)
- bisphosphonates (1)
- blebbing (1)
- blood banking (1)
- brain insulin signaling (1)
- burn injury (1)
- c. elegans (1)
- calcium (1)
- cancer cells (1)
- cell migration (1)
- cells (1)
- cerami-des (1)
- ceramides (1)
- cholesteryl ester (1)
- chronic kidney disease (1)
- chronic psychosocial stress (1)
- chronic subordinate colony housing (CSC) (1)
- circulation (1)
- click chemistry (1)
- colitis (1)
- collagen I (1)
- decitabine (1)
- dendritic cell (1)
- depressive-like behavior (1)
- diacylglycerol (1)
- disease (1)
- distress (1)
- drug delivery (1)
- drug design (1)
- drug metabolism (1)
- dysfunction (1)
- enzyme assays (1)
- enzymology (1)
- epigenetics (1)
- etanercept (1)
- experimental antigen-induced encephalomyelitis (1)
- extinction (1)
- fatty acid metabolism (1)
- fetal origins hypothesis (1)
- fibrosis (1)
- fingolimod (1)
- force-field (1)
- forebrain (1)
- functional inhibitors of acid sphin-gomyelinase (1)
- genes (1)
- glucocorticoid receptor (1)
- growth restriction (1)
- high density (1)
- hippocampus (1)
- human excised skin (1)
- hyperforin (1)
- immune (1)
- immunology (1)
- immunomodulator (1)
- immunonutrition (1)
- infection (1)
- inhibitory cytokines (1)
- integrins (1)
- interleukin-35 (1)
- intestine (1)
- invasion (1)
- keratinocytes (1)
- later health (1)
- life-span (1)
- linagliptin (1)
- lipid metabolism (1)
- lipid rafts (1)
- lipoproteins (1)
- liposomes (1)
- long chain base (1)
- lung cancer (1)
- lung infection (1)
- lung inflammation (1)
- lymphopenia (1)
- lyso-phospholipids (1)
- lysosomal hydrolases (1)
- lysosome (1)
- mass spectrometry (1)
- membrane fusion (1)
- membrane lipids (1)
- membrane repair (1)
- membrane-lipid therapy (1)
- menadione (1)
- microparticle (1)
- migration (1)
- mitochondria (1)
- molecular dynamics (1)
- molecular modeling (1)
- morpholino analogues of fingolimod (1)
- mortality (1)
- multiple sclerosis (1)
- n-acetyl-cysteine (1)
- nanogels (1)
- nanoparticles (1)
- nanotoxicology (1)
- neutral sphingomyelinase-2 (1)
- neutrophil chemotaxis (1)
- nutrient transport (1)
- operant behavior (1)
- oxidative stress (1)
- pH-sensitive nanoparticle (1)
- pH-sensitive nanoparticles (1)
- particle characterization (1)
- patterns (1)
- phagocytosis (1)
- plasma membrane (1)
- pneumococcal pneumonia (1)
- pregnancy (1)
- primary immunodeficiencies (1)
- proliferation (1)
- protein (1)
- proteomic analysis (1)
- refinement (1)
- repetitive elements (1)
- s-glutathionylation (1)
- serine palmitoyltransferase (1)
- skin equivalents (1)
- skin penetration (1)
- sphingolipid de novo synthesis (1)
- sphingolipid metabolism (1)
- sphingosine kinase (1)
- sphingosine kinase 1 (1)
- sphingosine kinase inhibitor SKI-II (1)
- sphingosine kinases (1)
- sphingosine-1-phosphate receptor 2 (1)
- stable-isotope labeling (1)
- storage (1)
- sulfotransferase (1)
- tacrolimus formulation (1)
- thermoresponsive-nanogel (1)
- thymosin beta 4 (1)
- topical (1)
- transfusion-related acute lung injury (1)
- transport proteins (1)
- tumor-metastasis (1)
- type 2 diabetes mellitus (1)
Institute
Drug loaded dendritic core-multishell (CMS) nanocarriers are of especial interest for the treatment of skin diseases, owing to their striking dermal delivery efficiencies following topical applications. CMS nanocarriers are composed of a polyglycerol core, connected by amide-bonds to an inner alkyl shell and an outer methoxy poly(ethylene glycol) shell. Since topically applied nanocarriers are subjected to biodegradation, the application of conventional amide-based CMS nanocarriers (10-A-18-350) has been limited by the potential production of toxic polyglycerol amines. To circumvent this issue, three tailored ester-based CMS nanocarriers (10-E-12-350, 10-E-15-350, 10-E-18-350) of varying inner alkyl chain length were synthesized and comprehensively characterized in terms of particle size, drug loading, biodegradation and dermal drug delivery efficiency. Dexamethasone (DXM), a potent drug widely used for the treatment of inflammatory skin diseases, was chosen as a therapeutically relevant test compound for the present study. Ester-and amide-based CMS nanocarriers delivered DXM more efficiently into human skin than a commercially available DXM cream. Subsequent in vitro and in vivo toxicity studies identified CMS (10-E-15-350) as the most biocompatible carrier system. The anti-inflammatory potency of DXM-loaded CMS (10-E-15-350) nanocarriers was assessed in TNF alpha supplemented skin models, where a significant reduction of the pro-inflammatory cytokine IL-8 was seen, with markedly greater efficacy than commercial DXM cream. In summary, we report the rational design and characterization of tailored, biodegradable, ester-based CMS nanocarriers, and their subsequent stepwise screening for biocompatibility, dermal delivery efficiency and therapeutic efficacy in a top-down approach yielding the best carrier system for topical applications. (C) 2016 Elsevier B.V. All rights reserved.
pH-sensitive nanoparticles which release in a controlled fashion on the skin or dissolve in the hair follicle could significantly improve treatment effectiveness and make transfollicular drug delivery a success. Dexamethasone-loaded Eudragit L 100 nanoparticles were prepared by nanoprecipitation from an organic drug-polymer solution. Their toxicity potential was assessed using isolated human fibroblasts. pH-dependent swelling and erosion kinetics of the nanoparticles were investigated by dynamic light scattering and viscosity measurements and its effect on drug release was assessed in vitro with Franz diffusion cells. Stable, 100-550 nm-sized dexamethasone-loaded Eudragit L 100 nanoparticles with drug loading capacity and entrapment efficiency as high as 83% and 85%, respectively, were obtained by using polyvinyl alcohol as a stabilizer and ethanol as organic solvent The nanoparticles showed little or no toxicity on isolated normal human fibroblasts. Dexamethasone existed in the nanoparticles as solid solution or in amorphous form. The nanoparticles underwent extensive swelling and slow drug release in media with a low buffer capacity (as low as 10 mM) and a higher pH or at a pH close to the dissolution pH of the polymer (pH 6) and a higher buffer capacity. In 40 mM buffer and above pH 6.8, the nanoparticles eroded fast or dissolved completely and thus released the drug rapidly. pH-sensitive nanoparticles which potentially release in a controlled manner on the stratum corneum but dissolve in the hair follicle could be prepared. (C) 2016 Elsevier B.V. All rights reserved.
Mutations in the gene encoding for filaggrin (FLG) are major predisposing factors for atopic dermatitis (AD). Besides genetic predisposition, immunological dysregulations considerably contribute to its pathophysiology. For example, thymic stromal lymphopoietin (TSLP) is highly expressed in lesional atopic skin and significantly contributes to the pathogenesis of AD by activating dendritic cells that then initiate downstream effects on, for example, T cells. However, little is known about the direct interplay between TSLP, filaggrin-deficient skin and other immune cells such as T lymphocytes. In the present study, FLG knockdown skin equivalents, characterised by intrinsically high TSLP levels, were exposed to activated CD4(+) T cells. T cell exposure resulted in an inflammatory phenotype of the skin equivalents. Furthermore, a distinct shift from a Th1/Th17 to a Th2/Th22 profile was observed following exposure of T cells to filaggrin-deficient skin equivalents. Interestingly, TSLP directly stimulated T cell migration exclusively in filaggrin-deficient skin equivalents even in the absence of dendritic cells, indicating a hitherto unknown role of TSLP in the pathogenesis of AD.
Nanoparticles can improve topical drug delivery: size, surface properties and flexibility of polymer nanoparticles are defining its interaction with the skin. Only few studies have explored skin penetration for one series of structurally related polymer particles with systematic alteration of material composition. Here, a series of rigid poly[acrylonitrile-co-(N-vinyl pyrrolidone)] model nanoparticles stably loaded with Nile Red or Rhodamin B, respectively, was comprehensively studied for biocompatibility and functionality. Surface properties were altered by varying the molar content of hydrophilic NVP from 0 to 24.1% and particle size ranged from 35 to 244 nm. Whereas irritancy and genotoxicity were not revealed, lipophilic and hydrophilic nanoparticles taken up by keratinocytes affected cell viability. Skin absorption of the particles into viable skin ex vivo was studied using Nile Red as fluorescent probe. Whilst an intact stratum corneum efficiently prevented penetration, almost complete removal of the horny layer allowed nanoparticles of smaller size and hydrophilic particles to penetrate into viable epidermis and dermis. Hence, systematic variations of nanoparticle properties allows gaining insights into critical criteria for biocompatibility and functionality of novel nanocarriers for topical drug delivery and risks associated with environmental exposure.
Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune disease of the central nervous system (CNS) which is associated with lower life expectancy and disability. The experimental antigen-induced encephalomyelitis (EAE) in mice is a useful animal model of MS, which allows exploring the etiopathogenetic mechanisms and testing novel potential therapeutic drugs. A new therapeutic paradigm for the treatment of MS was introduced in 2010 through the sphingosine 1-phosphate (S1P) analogue fingolimod (FTY720, Gilenya(R)), which acts as a functional S1P(1) antagonist on T lymphocytes to deplete these cells from the blood. In this study, we synthesized two novel structures, ST-1893 and ST-1894, which are derived from fingolimod and chemically feature a morpholine ring in the polar head group. These compounds showed a selective S1P(1) activation profile and a sustained S1P(1) internalization in cultures of S1P(1)-overexpressing Chinese hamster ovary (CHO)-K1 cells, consistent with a functional antagonism. In vivo, both compounds induced a profound lymphopenia in mice. Finally, these substances showed efficacy in the EAE model, where they reduced clinical symptoms of the disease, and, on the molecular level, they reduced the T-cell infiltration and several inflammatory mediators in the brain and spinal cord. In summary, these data suggest that S1P(1)-selective compounds may have an advantage over fingolimod and siponimod, not only in MS but also in other autoimmune diseases.
Bacterial pore-forming toxins compromise plasmalemmal integrity, leading to Ca2+ influx, leakage of the cytoplasm, and cell death. Such lesions can be repaired by microvesicular shedding or by the endocytic uptake of the injured membrane sites. Cells have at their disposal an entire toolbox of repair proteins for the identification and elimination of membrane lesions. Sphingomyelinases catalyze the breakdown of sphingomyelin into ceramide and phosphocholine. Sphingomyelin is predominantly localized in the outer leaflet, where it is hydrolyzed by acid sphingomyelinase (ASM) after lysosomal fusion with the plasma membrane. The magnesium-dependent neutral sphingomyelinase (NSM)-2 is found at the inner leaflet of the plasmalemma. Because either sphingomyelinase has been ascribed a role in the cellular stress response, we investigated their role in plasma membrane repair and cellular survival after treatment with the pore-forming toxins listeriolysin O (LLO) or pneumolysin (PLY). Jurkat T cells, in which ASM or NSM-2 was down-regulated [ASM knockdown (KD) or NSM-2 KD cells], showed inverse reactions to toxin-induced membrane damage: ASM KD cells displayed reduced toxin resistance, decreased viability, and defects in membrane repair. In contrast, the down-regulation of NSM-2 led to an increase in viability and enhanced plasmalemmal repair. Yet, in addition to the increased plasmalemmal repair, the enhanced toxin resistance of NSM-2 KD cells also appeared to be dependent on the activation of p38/MAPK, which was constitutively activated, whereas in ASM KD cells, the p38/MAPK activation was constitutively blunted.Schoenauer, R., Larpin, Y., Babiychuk, E. B., Drucker, P., Babiychuk, V. S., Avota, E., Schneider-Schaulies, S., Schumacher, F., Kleuser, B., Koffel, R., Draeger, A. Down-regulation of acid sphingomyelinase and neutral sphingomyelinase-2 inversely determines the cellular resistance to plasmalemmal injury by pore-forming toxins.
Liposomal FRET assay identifies potent drug-like inhibitors of the Ceramide Transport Protein (CERT)
(2020)
Ceramide transfer protein (CERT) mediates non-vesicular transfer of ceramide from endoplasmic reticulum to Golgi apparatus and thus catalyzes the rate-limiting step of sphingomyelin biosynthesis. Usually, CERT ligands are evaluated in tedious binding assays or non-homogenous transfer assays using radiolabeled ceramides. Herein, a facile and sensitive assay for CERT, based on Forster resonance energy transfer (FRET), is presented. To this end, we mixed donor and acceptor vesicles, each containing a different fluorescent ceramide species. By CERT-mediated transfer of fluorescent ceramide, a FRET system was established, which allows readout in 96-well plate format, despite the high hydrophobicity of the components. Screening of a 2 000 compound library resulted in two new potent CERT inhibitors. One is approved for use in humans and one is approved for use in animals. Evaluation of cellular activity by quantitative mass spectrometry and confocal microscopy showed inhibition of ceramide trafficking and sphingomyelin biosynthesis.
Sphingolipids are major components of the plasma membrane. In particular, ceramide serves as an essential building hub for complex sphingolipids, but also as an organizer of membrane domains segregating receptors and signalosomes. Sphingomyelin breakdown as a result of sphingomyelinase activation after ligation of a variety of receptors is the predominant source of ceramides released at the plasma membrane. This especially applies to T lymphocytes where formation of ceramide-enriched membrane microdomains modulates TCR signaling. Because ceramide release and redistribution occur very rapidly in response to receptor ligation, novel tools to further study these processes in living T cells are urgently needed. To meet this demand, we synthesized nontoxic, azido-functionalized ceramides allowing for bio-orthogonal click-reactions to fluorescently label incorporated ceramides, and thus investigate formation of ceramide-enriched domains. Azido-functionalized C-6-ceramides were incorporated into and localized within plasma membrane microdomains and proximal vesicles in T cells. They segregated into clusters after TCR, and especially CD28 ligation, indicating efficient sorting into plasma membrane domains associated with T cell activation; this was abolished upon sphingomyelinase inhibition. Importantly, T cell activation was not abrogated upon incorporation of the compound, which was efficiently excluded from the immune synapse center as has previously been seen in Ab-based studies using fixed cells. Therefore, the functionalized ceramides are novel, highly potent tools to study the subcellular redistribution of ceramides in the course of T cell activation. Moreover, they will certainly also be generally applicable to studies addressing rapid stimulation-mediated ceramide release in living cells.
Obligate human pathogenic Neisseria gonorrhoeae are the second most frequent bacterial cause of sexually transmitted diseases. These bacteria invade different mucosal tissues and occasionally disseminate into the bloodstream. Invasion into epithelial cells requires the activation of host cell receptors by the formation of ceramide-rich platforms. Here, we investigated the role of sphingosine in the invasion and intracellular survival of gonococci. Sphingosine exhibited an anti-gonococcal activity in vitro. We used specific sphingosine analogs and click chemistry to visualize sphingosine in infected cells. Sphingosine localized to the membrane of intracellular gonococci. Inhibitor studies and the application of a sphingosine derivative indicated that increased sphingosine levels reduced the intracellular survival of gonococci. We demonstrate here, that sphingosine can target intracellular bacteria and may therefore exert a direct bactericidal effect inside cells.
Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit.