{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:56:50Z","timestamp":1777517810354,"version":"3.51.4"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T00:00:00Z","timestamp":1355788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sphingosine\u20101\u2010phosphate (<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>1<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>) plays a crucial role in homeostasis of the immune system by regulating lymphocyte recirculation and inflammatory cell recruitment. The levels of <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>1<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> are tightly controlled through regulated production and controlled breakdown by sphingosine\u2010lyase (<jats:styled-content style=\"fixed-case\">SL<\/jats:styled-content>). The <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>1<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> analogue <jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>720 has been developed as an immunosuppressant in transplantation and tested as a treatment for various inflammatory diseases. <jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>720 exploits <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>1<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> biology by acting as a <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>1<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>1<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> 3 agonist and by inhibiting <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>1<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> breakdown by <jats:styled-content style=\"fixed-case\">SL<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Here, we investigate interfering <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>1<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> in allergic rhinitis (<jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>) and its way of action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Allergic rhinitis was induced by sensitizing mice to ovalbumin (<jats:styled-content style=\"fixed-case\">OVA<\/jats:styled-content>) and challenging the nose with <jats:styled-content style=\"fixed-case\">OVA<\/jats:styled-content> allergen. At the time of allergen challenge, mice received topical intranasal treatment with <jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>720. To address the relative contribution of <jats:styled-content style=\"fixed-case\">SL<\/jats:styled-content> inhibition in mediating its effects, some mice were treated with the <jats:styled-content style=\"fixed-case\">SL<\/jats:styled-content> inhibitor 2\u2010acetyl\u20104\u2010tetrahydroxybutyl (<jats:styled-content style=\"fixed-case\">THI<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>720 treatment resulted in significantly fewer eosinophils, mast cells and dendritic cells in the nasal mucosa of <jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content> animals, compared with diluent treatment. Levels of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013 produced by lymph node cells fell significantly in <jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>720\u2010treated animals. Moreover, <jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>720 proved potent enough to suppress inflammation in a model of persistent <jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>. <jats:italic>In vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experiments indicate that <jats:styled-content style=\"fixed-case\">FTY<\/jats:styled-content>720 impaired <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>h2 differentiation and proliferation important in driving eosinophilia and induced apoptosis in mast cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that interfering with <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>1<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content> metabolism is a powerful and feasible strategy to develop new topical agents that suppress <jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.12082","type":"journal-article","created":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T20:16:29Z","timestamp":1355861789000},"page":"204-212","source":"Crossref","is-referenced-by-count":21,"title":["Topical treatment targeting sphingosine\u20101\u2010phosphate and sphingosine lyase abrogates experimental allergic rhinitis in a murine model"],"prefix":"10.1111","volume":"68","author":[{"given":"A.","family":"KleinJan","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine Erasmus MC Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"van Nimwegen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Erasmus MC Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Leman","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Erasmus MC Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. C.","family":"Hoogsteden","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Erasmus MC Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. N.","family":"Lambrecht","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Erasmus MC Rotterdam The Netherlands"},{"name":"Department of Molecular Biomedical Research VIB, Wijnaarde Gent Belgium"},{"name":"Laboratory of Immunoregulation and Mucosal Immunology, Department of Respiratory Medicine University of Gent Gent Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,12,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-001-0007-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000319297"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.05.030"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2000.00827.x"},{"key":"e_1_2_9_6_1","first-page":"414","article-title":"Immunotherapy with recombinant house dust mite group 2 allergen vaccine inhibits allergic airway inflammation in mice","volume":"24","author":"Yu HQ","year":"2006","journal-title":"Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042311"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00645.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28295"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.6206"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113640"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201142018"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.4.2458"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.09.016"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.6.4323"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.11.8010"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellbi.2009.02.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.1996.tb00594.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2008.03.001"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7636"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.1992.tb00194.x"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fall.12082","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.12082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T15:27:51Z","timestamp":1700666871000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.12082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,18]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,2]]}},"alternative-id":["10.1111\/all.12082"],"URL":"https:\/\/doi.org\/10.1111\/all.12082","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,18]]}}}