{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:25:43Z","timestamp":1780503943802,"version":"3.54.1"},"reference-count":57,"publisher":"Walter de Gruyter GmbH","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pulmonary infections of cystic fibrosis (CF) patients with <jats:italic>Staphylococcus aureus<\/jats:italic> (<jats:italic>S. aureus<\/jats:italic>) occur very early in the disease. The molecular details that cause infection-susceptibility of CF patients to and mediate infection with <jats:italic>S. aureus<\/jats:italic> are poorly characterized. Therefore, we aimed to identify the role of \u03b1-toxin, a major <jats:italic>S. aureus<\/jats:italic> toxin, for pulmonary infection of CF mice. Infection with <jats:italic>S. aureus<\/jats:italic> JE2 resulted in severe pneumonia in CF mice, while wildtype mice were almost unaffected. Deficiency of \u03b1-toxin in JE2-\u0394hla reduced the pathogenicity of <jats:italic>S. aureus<\/jats:italic> in CF mice. However, CF mice were still more susceptible to the mutant <jats:italic>S. aureus<\/jats:italic> strain than wildtype mice. The <jats:italic>S. aureus<\/jats:italic> JE2 induced a marked increase of ceramide and a downregulation of sphingosine and acid ceramidase expression in bronchi of CF mice. Deletion of \u03b1-toxin reduced these changes after infection of CF mice. Similar changes were observed in wildtype mice, but at much lower levels. Our data indicate that expression of \u03b1-toxin is a major factor causing <jats:italic>S. aureus<\/jats:italic> infections in CF mice. Wildtype <jats:italic>S. aureus<\/jats:italic> induces a marked increase of ceramide and a reduction of sphingosine and acid ceramidase expression in bronchial epithelial cells of wildtype and CF mice, changes that determine infection susceptibility.<\/jats:p>","DOI":"10.1515\/hsz-2018-0161","type":"journal-article","created":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T15:20:32Z","timestamp":1522855232000},"page":"1203-1213","source":"Crossref","is-referenced-by-count":18,"title":["Pulmonary infection of cystic fibrosis mice with <i>Staphylococcus aureus<\/i> requires expression of \u03b1-toxin"],"prefix":"10.1515","volume":"399","author":[{"given":"Simone","family":"Keitsch","sequence":"first","affiliation":[{"name":"Department of Molecular Biology , Medical School , University of Duisburg-Essen , Hufelandstrasse 55 , D-45122 Essen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Riethm\u00fcller","sequence":"additional","affiliation":[{"name":"Center for Pediatric Clinical Studies, Children\u2019s Clinic , University of T\u00fcbingen, Hoppe-Seyler-Str. 1 , D-72076 T\u00fcbingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Soddemann","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology , Medical School , University of Duisburg-Essen , Hufelandstrasse 55 , D-45122 Essen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Sehl","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology , Medical School , University of Duisburg-Essen , Hufelandstrasse 55 , D-45122 Essen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Wilker","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology , Medical School , University of Duisburg-Essen , Hufelandstrasse 55 , D-45122 Essen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Surgery , University of Cincinnati , College of Medicine , 231 Albert Sabin Way , Cincinnati, OH 45267-0558 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles C.","family":"Caldwell","sequence":"additional","affiliation":[{"name":"Department of Surgery , University of Cincinnati , College of Medicine , 231 Albert Sabin Way , Cincinnati, OH 45267-0558 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Fraunholz","sequence":"additional","affiliation":[{"name":"Chair of Microbiology , University of W\u00fcrzburg, Am Hubland , D-97074 W\u00fcrzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Gulbins","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology , Medical School , University of Duisburg-Essen , Hufelandstrasse 55 , D-45122 Essen , Germany"},{"name":"Department of Surgery , University of Cincinnati , College of Medicine , 231 Albert Sabin Way , Cincinnati, OH 45267-0558 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin Anne","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology , Medical School , University of Duisburg-Essen , Hufelandstrasse 55 , D-45122 Essen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2018,5,1]]},"reference":[{"key":"2023040406465657751_j_hsz-2018-0161_ref_001_w2aab3b7c12b1b6b1ab2b1b1Aa","doi-asserted-by":"crossref","unstructured":"Adams, C., Icheva, V., Deppisch, C., Lauer, J., Herrmann, G., Graepler-Mainka, U., Heyder, S., Gulbins, E., and Riethmueller, J. (2016). Long-term pulmonal therapy of cystic fibrosis-patients with amitriptyline. Cell. Physiol. Biochem. 39, 565\u2013572.","DOI":"10.1159\/000445648"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_002_w2aab3b7c12b1b6b1ab2b1b2Aa","doi-asserted-by":"crossref","unstructured":"Becker, K.A., Riethm\u00fcller, J., L\u00fcth, A., D\u00f6ring, G., Kleuser, B., and Gulbins, E. (2010). Acid sphingomyelinase inhibitors normalize pulmonary ceramide and inflammation in cystic fibrosis. Am. J. Respir. Cell. Mol. Biol. 42, 716\u2013724.","DOI":"10.1165\/rcmb.2009-0174OC"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_003_w2aab3b7c12b1b6b1ab2b1b3Aa","doi-asserted-by":"crossref","unstructured":"Becker, K.A., Henry, B., Ziobro, R., T\u00fcmmler, B., Gulbins, E., and Grassm\u00e9, H. (2012). Role of CD95 in pulmonary inflammation and infection in cystic fibrosis. J. Mol. Med. (Berl.) 90, 1011\u20131023.","DOI":"10.1007\/s00109-012-0867-2"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_004_w2aab3b7c12b1b6b1ab2b1b4Aa","doi-asserted-by":"crossref","unstructured":"Bibel, D.J., Aly, R., and Shinefield, H.R. (1992). Antimicrobial activity of sphingosines. J. Invest. Dermatol. 98, 269\u2013273.","DOI":"10.1111\/1523-1747.ep12497842"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_005_w2aab3b7c12b1b6b1ab2b1b5Aa","doi-asserted-by":"crossref","unstructured":"Bodas, M., Min, T., Mazur, S., and Vij, N. (2011). Critical modifier role of membrane-cystic fibrosis transmembrane conductance regulator-dependent ceramide signaling in lung injury and emphysema. J. Immunol. 186, 602\u2013613.","DOI":"10.4049\/jimmunol.1002850"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_006_w2aab3b7c12b1b6b1ab2b1b6Aa","doi-asserted-by":"crossref","unstructured":"Bonfield, T.L., Konstan, M.W., Burfeind, P., Panuska, J.R., Hilliard, J.B., and Berger, M. (1995). Normal bronchial epithelial cells constitutively produce the anti-inflammatory cytokine interleukin-10, which is downregulated in cystic fibrosis. Am. J. Respir. Cell. Mol. Biol. 13, 257\u2013261.","DOI":"10.1165\/ajrcmb.13.3.7544594"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_007_w2aab3b7c12b1b6b1ab2b1b7Aa","doi-asserted-by":"crossref","unstructured":"Brodlie, M., McKean, M.C., Johnson, G.E., Gray, J., Fisher, A.J., Corris, P.A., Lordan, J.L., and Ward, C. (2010). Ceramide is increased in the lower airway epithelium of people with advanced cystic fibrosis lung disease. Am. J. Respir. Crit. Care Med. 182, 369\u2013375.","DOI":"10.1164\/rccm.200905-0799OC"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_008_w2aab3b7c12b1b6b1ab2b1b8Aa","doi-asserted-by":"crossref","unstructured":"Bubeck Wardenburg, J., Patel, R.J., and Schneewind, O. (2007). Surface proteins and exotoxins are required for the pathogenesis of Staphylococcus aureus pneumonia. Infect. Immun. 75, 1040\u20131044.","DOI":"10.1128\/IAI.01313-06"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_009_w2aab3b7c12b1b6b1ab2b1b9Aa","doi-asserted-by":"crossref","unstructured":"Caretti, A., Bragonzi, A., Facchini, M., De Fino, I., Riva, C., Gasco, P., Musicanti, C., Casas, J., Fabri\u00e0s, G., Ghidoni, R., et al. (2014). Anti-inflammatory action of lipid nanocarrier-delivered myriocin: therapeutic potential in cystic fibrosis. Biochim. Biophys. Acta 1840, 586\u2013594.","DOI":"10.1016\/j.bbagen.2013.10.018"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_010_w2aab3b7c12b1b6b1ab2b1c10Aa","doi-asserted-by":"crossref","unstructured":"Caretti, A., Vasso, M., Bonezzi, F.T., Gallina, A., Trinchera, M., Rossi, A., Adami, R., Casas, J., Falleni, M., Tosi, D., et al. (2017). Myriocin treatment of CF lung infection and inflammation: complex analyses for enigmatic lipids. Naunyn-Schmiedeberg\u2018s Arch. Pharmacol. 390, 775\u2013790.","DOI":"10.1007\/s00210-017-1373-4"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_011_w2aab3b7c12b1b6b1ab2b1c11Aa","doi-asserted-by":"crossref","unstructured":"Charizopoulou, N., Jansen, S., Dorsch, M., Stanke, F., Dorin, J.R., Hedrich, H.J., and T\u00fcmmler, B. (2004). Instability of the insertional mutation in CftrTgH(neoim)Hgu cystic fibrosis mouse model. BMC Genet. 5, 6.","DOI":"10.1186\/1471-2156-5-6"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_012_w2aab3b7c12b1b6b1ab2b1c12Aa","doi-asserted-by":"crossref","unstructured":"Charizopoulou, N., Wilke, M., Dorsch, M., Bot, A., Jorna, H., Jansen, S., Stanke, F., Hedrich, H.J., de Jonge, H.R., and T\u00fcmmler, B. (2006). Spontaneous rescue from cystic fibrosis in a mouse model. BMC Genet. 7, 18.","DOI":"10.1186\/1471-2156-7-18"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_013_w2aab3b7c12b1b6b1ab2b1c13Aa","doi-asserted-by":"crossref","unstructured":"Di, A., Brown, M.E., Deriy, L.V., Li, C., Szeto, F.L., Chen, Y., Huang, P., Tong, J., Naren, A.P., Bindokas, V., et al. (2006). Cftr regulates phagosome acidification in macrophages and alters bactericidal activity. Nat. Cell Biol. 8, 933\u2013944.","DOI":"10.1038\/ncb1456"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_014_w2aab3b7c12b1b6b1ab2b1c14Aa","doi-asserted-by":"crossref","unstructured":"Elborn, J.S. (2016). Cystic fibrosis. Lancet 388, 2519\u20132531.","DOI":"10.1016\/S0140-6736(16)00576-6"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_015_w2aab3b7c12b1b6b1ab2b1c15Aa","doi-asserted-by":"crossref","unstructured":"Esen, M., Schreiner, B., Jendrossek, V., Lang, F., Fassbender, K., Grassm\u00e9, H., and Gulbins, E. (2001). Mechanisms of Staphylococcus aureus induced apoptosis of human endothelial cells. Apoptosis 6, 431\u2013439.","DOI":"10.1023\/A:1012445925628"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_016_w2aab3b7c12b1b6b1ab2b1c16Aa","doi-asserted-by":"crossref","unstructured":"Fey, P.D., Endres, J.L., Yajjala, V.K., Widhelm, T.J., Boissy, R.J., Bose, J.L., and Bayles, K.W. (2013). A genetic resource for rapid and comprehensive phenotype screening of nonessential Staphylococcus aureus genes. MBio 4, e00537\u2013e00512.","DOI":"10.1128\/mBio.00537-12"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_017_w2aab3b7c12b1b6b1ab2b1c17Aa","doi-asserted-by":"crossref","unstructured":"Fischer, C.L., Drake, D.R., Dawson, D.V., Blanchette, D.R., Brogden, K.A., and Wertz, P.W. (2012). Antibacterial activity of sphingoid bases and fatty acids against gram-positive and gram-negative bacteria. Antimicrob. Agents Chemother. 56, 1157\u20131161.","DOI":"10.1128\/AAC.05151-11"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_018_w2aab3b7c12b1b6b1ab2b1c18Aa","doi-asserted-by":"crossref","unstructured":"Forbes, A.R. and Horrigan, R.W. (1977). Mucociliary flow in the trachea during anesthesia with enflurane, ether, nitrous oxide, and morphine. Anesthesiology 146, 319\u2013321.","DOI":"10.1097\/00000542-197705000-00002"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_019_w2aab3b7c12b1b6b1ab2b1c19Aa","doi-asserted-by":"crossref","unstructured":"Gari\u0107, D., De Sanctis, J.B., Wojewodka, G., Houle, D., Cupri, S., Abu-Arish, A., Hanrahan, J.W., Hajduch, M., Matouk, E., and Radzioch, D. (2017). Fenretinide differentially modulates the levels of long- and very long-chain ceramidesby downregulating Cers5 enzyme: evidence from bench to bedside. J. Mol. Med. (Berl). 95, 1053\u20131064.","DOI":"10.1007\/s00109-017-1564-y"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_020_w2aab3b7c12b1b6b1ab2b1c20Aa","doi-asserted-by":"crossref","unstructured":"Grassm\u00e9, H., Kirschnek, S., Riethmueller, J., Riehle, A., von K\u00fcrthy, G., Lang, F., Weller, M., and Gulbins, E. (2000). CD95\/CD95 ligand interactions on epithelial cells in host defense to Pseudomonas aeruginosa. Science 290, 527\u2013530.","DOI":"10.1126\/science.290.5491.527"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_021_w2aab3b7c12b1b6b1ab2b1c21Aa","doi-asserted-by":"crossref","unstructured":"Grassm\u00e9, H., Jekle, A., Riehle, A., Schwarz, H., Berger, J., Sandhoff, K., Kolesnick, R., and Gulbins, E. (2001). CD95 signaling via ceramide-rich membrane rafts. J. Biol. Chem. 276, 20589\u201320596.","DOI":"10.1074\/jbc.M101207200"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_022_w2aab3b7c12b1b6b1ab2b1c22Aa","doi-asserted-by":"crossref","unstructured":"Grassm\u00e9, H., Jendrossek, V., Riehle, A., von Kurthy, G., Berger, J., Schwarz, H., Weller, M., Kolesnick, R., and Gulbins, E. (2003). Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts. Nat. Med. 9, 322\u2013330.","DOI":"10.1038\/nm823"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_023_w2aab3b7c12b1b6b1ab2b1c23Aa","doi-asserted-by":"crossref","unstructured":"Grassm\u00e9, H., Henry, B., Ziobro, R., Becker, K.A., Riethm\u00fcller, J., Gardner, A., Seitz, A.P., Steinmann, J., Lang, S., Ward, C., et al. (2017). \u03b21-Integrin accumulates in cystic fibrosis luminal airway epithelial membranes and decreases sphingosine, promoting bacterial infections. Cell. Host. Microbe 21, 707\u2013718.","DOI":"10.1016\/j.chom.2017.05.001"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_024_w2aab3b7c12b1b6b1ab2b1c24Aa","doi-asserted-by":"crossref","unstructured":"Gulbins, E., Palmada, M., Reichel, M., L\u00fcth, A., B\u00f6hmer, C., Amato, D., M\u00fcller, C.P., Tischbirek, C.H., Groemer, T.W., Tabatabai, G., et al. (2013). Acid sphingomyelinase\/ceramide system mediates effects of antidepressant drugs. Nat. Med. 19, 934\u2013938.","DOI":"10.1038\/nm.3214"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_025_w2aab3b7c12b1b6b1ab2b1c25Aa","doi-asserted-by":"crossref","unstructured":"Hurwitz, R., Ferlinz, K., and Sandhoff, K. (1994). The tricyclic anti-depressant desipramine causes proteolytic degradation of lysosomal sphingo-myelinase in human fibroblasts. Biol. Chem. Hoppe-Seyler 375, 447\u2013450.","DOI":"10.1515\/bchm3.1994.375.7.447"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_026_w2aab3b7c12b1b6b1ab2b1c26Aa","doi-asserted-by":"crossref","unstructured":"Inoshima, I., Inoshima, N., Wilke, G.A., Powers, M.E., Frank, K.M., Wang, Y., and Bubeck Wardenburg, J. (2011). A Staphylococcus aureus pore-forming toxin subverts the activity of ADAM10 to cause lethal infection in mice. Nat. Med. 17, 1310\u20131314.","DOI":"10.1038\/nm.2451"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_027_w2aab3b7c12b1b6b1ab2b1c27Aa","doi-asserted-by":"crossref","unstructured":"Inoshima, N., Wang, Y., and Bubeck Wardenburg, J. (2012). Genetic requirement for ADAM10 in severe Staphylococcus aureus skin infection. J. Invest. Dermatol. 132, 1513\u20131516.","DOI":"10.1038\/jid.2011.462"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_028_w2aab3b7c12b1b6b1ab2b1c28Aa","doi-asserted-by":"crossref","unstructured":"Inoue, H., Massion, P.P., Ueki, I.F., Grattan, K.M., Hara, M., Dohrman, A.F., Chan, B., Lausier, J.A., Golden, J.A., and Nadel, J.A. (1994). Pseudomonas stimulates interleukin-8 mRNA expression selectively in airway epithelium, in gland ducts, and in recruited neutrophils. Am. J. Respir. Cell. Mol. Biol. 11, 651\u2013663.","DOI":"10.1165\/ajrcmb.11.6.7946394"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_029_w2aab3b7c12b1b6b1ab2b1c29Aa","doi-asserted-by":"crossref","unstructured":"Kerem, B., Rommens, J.M., Buchanan, J.A., Markiewicz, D., Cox, T.K., Chakravarti, A., Buchwald, M., and Tsui, L.C. (1989). Identification of the cystic fibrosis gene: genetic analysis. Science 245, 1073\u20131080.","DOI":"10.1126\/science.2570460"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_030_w2aab3b7c12b1b6b1ab2b1c30Aa","doi-asserted-by":"crossref","unstructured":"Khan, T.Z., Wagener, J.S., Bost, T., Martinez, J., Accurso, F.J., and Riches, D.W. (1995). Early pulmonary inflammation in infants with cystic fibrosis. Am. J. Respir. Crit. Care Med. 151, 1075\u20131082.","DOI":"10.1164\/ajrccm.151.4.7697234"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_031_w2aab3b7c12b1b6b1ab2b1c31Aa","doi-asserted-by":"crossref","unstructured":"Kornhuber, J., Tripal, P., Reichel, M., Terfloth, L., Bleich, S., Wiltfang, J., and Gulbins, E. (2008). Identification of new functional inhibitors of acid sphingomyelinase using a structure-property-activity relation model. J. Med. Chem. 51, 219\u2013237.","DOI":"10.1021\/jm070524a"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_032_w2aab3b7c12b1b6b1ab2b1c32Aa","doi-asserted-by":"crossref","unstructured":"Kornhuber, J., Tripal, P., Reichel, M., M\u00fchle, C., Rhein, C., M\u00fchlbacher, M., Groemer, T.W., and Gulbins, E. (2010). Functional inhibitors of acid sphingomyelinase (FIASMAs): a novel pharmacological group of drugs with broad clinical applications. Cell. Physiol. Biochem. 26, 9\u201320.","DOI":"10.1159\/000315101"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_033_w2aab3b7c12b1b6b1ab2b1c33Aa","doi-asserted-by":"crossref","unstructured":"Li, C., Wu, Y., Orian-Rousseau, V., Zhang, Y., Gulbins, E., and Grassm\u00e9, H. (2017a). Regulation of Staphylococcus aureus infection of macrophages by CD44, reactive oxygen species and acid sphingomyelinase. Antioxid. Redox Signal. doi: 10.1089\/ars.2017.6994.","DOI":"10.1089\/ars.2017.6994"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_034_w2aab3b7c12b1b6b1ab2b1c34Aa","doi-asserted-by":"crossref","unstructured":"Li, C., Wu, Y., Riehle, A., Ma, J., Kamler, M., Gulbins, E., and Grassm\u00e9, H. (2017b). Staphylococcus survives in cystic fibrosis macrophages forming a reservoir for chronic pneumonia. Infect. Immun. 85, e00883\u2013e00816.","DOI":"10.1128\/IAI.00883-16"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_035_w2aab3b7c12b1b6b1ab2b1c35Aa","doi-asserted-by":"crossref","unstructured":"Locke, L.W., Myerburg, M.M., Weiner, D.J., Markovetz, M.R., Parker, R.S., Muthukrishnan, A., Weber, L., Czachowski, M.R., Lacy, R.T., Pilewski, J.M., et al. (2016). Pseudomonas infection and mucociliary and absorptive clearance in the cystic fibrosis lung. Eur. Respir. J. 47, 1392\u20131401.","DOI":"10.1183\/13993003.01880-2015"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_036_w2aab3b7c12b1b6b1ab2b1c36Aa","doi-asserted-by":"crossref","unstructured":"Lyczak, J.B., Cannon, C.L., and Pier, G.B. (2001). Lung infections associated with cystic fibrosis. Clin. Microbiol. Rev. 15, 194\u2013222.","DOI":"10.1128\/CMR.15.2.194-222.2002"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_037_w2aab3b7c12b1b6b1ab2b1c37Aa","doi-asserted-by":"crossref","unstructured":"Matsui, H., Grubb, B.R., Tarran, R., Randell, S.H., Gatzy, J.T., Davis, C.W., and Boucher, R.C. (1998). Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell 95, 1005\u20131015.","DOI":"10.1016\/S0092-8674(00)81724-9"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_038_w2aab3b7c12b1b6b1ab2b1c38Aa","doi-asserted-by":"crossref","unstructured":"Matsui, H., Verghese, M.W., Kesimer, M., Schwab, U.E., Randell, S.H., Sheehan, J.K., Grubb, B.R., and Boucher, R.C. (2005). Reduced three-dimensional motility in dehydrated airway mucus prevents neutrophil capture and killing bacteria on airway epithelial surfaces. J. Immunol. 175, 1090\u20131099.","DOI":"10.4049\/jimmunol.175.2.1090"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_039_w2aab3b7c12b1b6b1ab2b1c39Aa","doi-asserted-by":"crossref","unstructured":"N\u00e4hrlich, L., Mainz, A., Unger, K., Graepler-Mainka, U., Hector, A., Heyder, S., Stern, M., D\u00f6ring, G., Gulbins, E., and Riethm\u00fcller, J. (2013). Therapy of CF-patients with amitriptyline and placebo \u2013 a randomised, double-blind, placebo-controlled phase IIb multicenter, cohort study. Cell. Physiol. Biochem. 31, 505\u2013512.","DOI":"10.1159\/000350071"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_040_w2aab3b7c12b1b6b1ab2b1c40Aa","doi-asserted-by":"crossref","unstructured":"Oceandy, D., McMorran, B.J., Smith, S.N., Schreiber, R., Kunzelmann, K., Alton, E.W., Hume, D.A., and Wainwright, B.J. (2002). Gene complementation of airway epithelium in the cystic fibrosis mouse is necessary and sufficient to correct the pathogen clearance and inflammatory abnormalities. Hum. Mol. Genet. 11, 1059\u20131067.","DOI":"10.1093\/hmg\/11.9.1059"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_041_w2aab3b7c12b1b6b1ab2b1c41Aa","doi-asserted-by":"crossref","unstructured":"Okino, N., He, X., Gatt, S., Sandhoff, K., Ito, M., and Schuchman, E.H. (2003). The reverse activity of human acid ceramidase. J. Biol. Chem. 278, 29948\u201329953.","DOI":"10.1074\/jbc.M303310200"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_042_w2aab3b7c12b1b6b1ab2b1c42Aa","doi-asserted-by":"crossref","unstructured":"Peng, H., Li, C., Kadow, S., Henry, B.D., Steinmann, J., Becker, K.A., Riehle, A., Beckmann, N., Wilker, B., Li, P.L., et al. (2015). Acid sphingomyelinase inhibition protects mice from lung edema and lethal Staphylococcus aureus sepsis. J. Mol. Med. (Berl). 93, 675\u2013689.","DOI":"10.1007\/s00109-014-1246-y"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_043_w2aab3b7c12b1b6b1ab2b1c43Aa","doi-asserted-by":"crossref","unstructured":"Pewzner-Jung, Y., Tavakoli Tabazavareh, S., Grassm\u00e9, H., Becker, K.A., Japtok, L., Steinmann, J., Joseph, T., Lang, S., Tuemmler, B., Schuchman, E.H., et al. (2014). Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa. EMBO Mol. Med. 6, 1205\u20131214.","DOI":"10.15252\/emmm.201404075"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_044_w2aab3b7c12b1b6b1ab2b1c44Aa","doi-asserted-by":"crossref","unstructured":"Powers, M.E., Kim, H.K., Wang, Y., and Bubeck Wardenburg, J. (2012). ADAM10 mediates vascular injury induced by Staphylococcus aureus \u03b1-hemolysin. J. Infect. Dis. 206, 352\u2013356.","DOI":"10.1093\/infdis\/jis192"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_045_w2aab3b7c12b1b6b1ab2b1c45Aa","doi-asserted-by":"crossref","unstructured":"Quinn, R.A., Lim, Y.W., Mak, T.D., Whiteson, K., Furlan, M., Conrad, D., Rohwer, F., and Dorrestein, P. (2016). Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease. Peer J. 4, e2174.","DOI":"10.7717\/peerj.2174"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_046_w2aab3b7c12b1b6b1ab2b1c46Aa","doi-asserted-by":"crossref","unstructured":"Riethm\u00fcller, J., Anthonysamy, J., Serra, E., Schwab, M., D\u00f6ring, G., and Gulbins, E. (2009). Therapeutic efficacy and safety of amitriptyline in patients with cystic fibrosis. Cell. Physiol. Biochem. 24, 65\u201372.","DOI":"10.1159\/000227814"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_047_w2aab3b7c12b1b6b1ab2b1c47Aa","doi-asserted-by":"crossref","unstructured":"Riordan, J.R., Rommens, J.M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J.L., et al. (1989). Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245, 1066\u20131073.","DOI":"10.1126\/science.2475911"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_048_w2aab3b7c12b1b6b1ab2b1c48Aa","doi-asserted-by":"crossref","unstructured":"Rommens, J.M., Iannuzzi, M.C., Kerem, B., Drumm, M.L., Melmer, G., Dean, M., Rozmahel, R., Cole, J.L., Kennedy, D., Hidaka, N., et al. (1989). Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245, 1059\u20131065.","DOI":"10.1126\/science.2772657"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_049_w2aab3b7c12b1b6b1ab2b1c49Aa","doi-asserted-by":"crossref","unstructured":"Schultz, M.J., Rijneveld, A.W., Florquin, S., Edwards, C.K., Dinarello, C.A., and van der Poll, T. (2002). Role of interleukin-1 in the pulmonary immune response during Pseudomonas aeruginosa pneumonia. Am. J. Physiol. Lung. Cell. Mol. Physiol. 282, L285\u2013L290.","DOI":"10.1152\/ajplung.00461.2000"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_050_w2aab3b7c12b1b6b1ab2b1c50Aa","doi-asserted-by":"crossref","unstructured":"Tabary, O., Escotte, S., Couetil, J.P., Hubert, D., Dusser, D., Puchelle, E., and Jacquot, J. (2001). Relationship between I\u03baB\u03b1 deficiency, NF-\u03baB activity and interleukin-8 production in CF human airway epithelial cells. Pfl\u00fcger\u2019s Arch. 443, S40\u2013S44.","DOI":"10.1007\/s004240100642"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_051_w2aab3b7c12b1b6b1ab2b1c51Aa","doi-asserted-by":"crossref","unstructured":"Tavakoli Tabazavareh, S., Seitz, A., Jernigan, P., Sehl, C., Keitsch, S., Lang, S., Kahl, B.C., Edwards, M., Grassm\u00e9, H., Gulbins, E., et al. (2016). Lack of sphingosine causes susceptibility to pulmonary Staphylococcus aureus infections in cystic fibrosis. Cell. Physiol. Biochem. 38, 2094\u20132102.","DOI":"10.1159\/000445567"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_052_w2aab3b7c12b1b6b1ab2b1c52Aa","doi-asserted-by":"crossref","unstructured":"Teichgr\u00e4ber, V., Ulrich, M., Endlich, N., Riethm\u00fcller, J., Wilker, B., De Oliveira-Munding, C.C., van Heeckeren, A.M., Barr, M.L., von K\u00fcrthy, G., Schmid, K.W., et al. (2008). Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat. Med. 14, 382\u2013391.","DOI":"10.1038\/nm1748"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_053_w2aab3b7c12b1b6b1ab2b1c53Aa","doi-asserted-by":"crossref","unstructured":"Tirouvanziam, R., de Bentzmann, S., Hubeau, C., Hinnrasky, J., Jacquot, J., Peault, B., and Puchelle, E. (2000). Inflammation and infection in naive human cystic fibrosis airway grafts. Am. J. Respir. Cell. Mol. Biol. 23, 121\u2013127.","DOI":"10.1165\/ajrcmb.23.2.4214"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_054_w2aab3b7c12b1b6b1ab2b1c54Aa","doi-asserted-by":"crossref","unstructured":"Ulrich, M., Worlitzsch, D., Viglio, S., Siegmann, N., Iadarola, P., Shute, J.K., Geiser, M., Pier, G.B., Friedel, G., Barr, M.L., et al. (2010). Alveolar inflammation in cystic fibrosis. J. Cyst. Fibros. 9, 217\u2013227.","DOI":"10.1016\/j.jcf.2010.03.001"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_055_w2aab3b7c12b1b6b1ab2b1c55Aa","doi-asserted-by":"crossref","unstructured":"Verhaeghe, C., Delbecque, K., de Leval, L., Oury, C., and Bours, V. (2007). Early inflammation in the airways of a cystic fibrosis foetus. J. Cyst. Fibros. 6, 304\u2013308.","DOI":"10.1016\/j.jcf.2006.12.001"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_056_w2aab3b7c12b1b6b1ab2b1c56Aa","doi-asserted-by":"crossref","unstructured":"Wilke, G.A. and Bubeck Wardenburg, J. (2010). Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus \u03b1-hemolysin-mediated cellular injury. Proc. Natl. Acad. Sci. USA 107, 13473\u201313478.","DOI":"10.1073\/pnas.1001815107"},{"key":"2023040406465657751_j_hsz-2018-0161_ref_057_w2aab3b7c12b1b6b1ab2b1c57Aa","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, X., Grassm\u00e9, H., D\u00f6ring, G., and Gulbins, E. (2009). Alterations in ceramide concentration and pH determine the release of reactive oxygen species by Cftr-deficient macrophages on infection. J. Immunol. 184, 5104\u20135111.","DOI":"10.4049\/jimmunol.0902851"}],"container-title":["Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.degruyter.com\/view\/j\/bchm.2018.399.issue-10\/hsz-2018-0161\/hsz-2018-0161.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/hsz-2018-0161\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/hsz-2018-0161\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T07:20:53Z","timestamp":1680592853000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/hsz-2018-0161\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,1]]},"references-count":57,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,6,21]]},"published-print":{"date-parts":[[2018,9,25]]}},"alternative-id":["10.1515\/hsz-2018-0161"],"URL":"https:\/\/doi.org\/10.1515\/hsz-2018-0161","relation":{},"ISSN":["1437-4315","1431-6730"],"issn-type":[{"value":"1437-4315","type":"electronic"},{"value":"1431-6730","type":"print"}],"subject":[],"published":{"date-parts":[[2018,5,1]]}}}