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Prior work suggests that IL\u20104 alleviates ifosfamide\u2010induced hemorrhagic cystitis (IHC), but systemically administered IL\u20104 causes significant side effects. We hypothesized that the\n                    <jats:italic>Schistosoma hematobium<\/jats:italic>\n                    homolog of IL\u20104\u2010inducing principle from\n                    <jats:italic>Schistosoma mansoni<\/jats:italic>\n                    eggs (H\u2010IPSE), would reduce IHC and associated bladder pathology. IPSE binds IgE on basophils and mast cells, triggering IL\u20104 secretion by these cells. IPSE is also an \u201cinfiltrin,\u201d translocating into the host nucleus to modulate gene transcription. Mice were administered IL\u20104, H\u2010IPSE protein or its nuclear localization sequence (NLS) mutant, with or without neutralizing anti\u2010IL\u20104 antibody, or 2\u2010mercaptoethane sulfonate sodium (MESNA; a drug used to prevent IHC), followed by ifosfamide. Bladder tissue damage and hemoglobin content were measured. Spontaneous and evoked pain, urinary frequency, and bladdergene expression analysis were assessed. Pain behaviors were interpreted in a blinded fashion. One dose of H\u2010IPSE was superior to MESNA and IL\u20104 in suppressing bladder hemorrhage in an IL\u20104\u2010dependent fashion and comparable with MESNA in dampening ifosfamide\u2010triggered pain behaviors in an NLS\u2010dependent manner. H\u2010IPSE also accelerated urothelial repair following IHC. Our work represents the first therapeutic exploitation of a uropathogen\u2010derived host modulatory molecule in a clinically relevant bladder disease model and indicates that IPSE may be an alternative to MESNA for mitigating CHC.\u2014Mbanefo, E. C., Le, L., Pennington, L. F., Odegaard, J. I., Jardetzky, T. S., Alouffi, A., Falcone, F. H., Hsieh, M. H. Therapeutic exploitation of IPSE, a urogenital parasite\u2010derived host modulatory protein, for chemotherapy\u2010induced hemorrhagic cystitis.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 32, 4408\u20134419 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701415r","type":"journal-article","created":{"date-parts":[[2018,4,3]],"date-time":"2018-04-03T13:53:57Z","timestamp":1522763637000},"page":"4408-4419","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Therapeutic exploitation of IPSE, a urogenital parasite\u2010derived host modulatory protein, for chemotherapy\u2010induced hemorrhagic cystitis"],"prefix":"10.1096","volume":"32","author":[{"given":"Evaristus C.","family":"Mbanefo","sequence":"first","affiliation":[{"name":"Bladder Immunology Group Biomedical Research Institute Rockville Maryland USA"},{"name":"Division of Urology Children's National Medical Center Washington District of Columbia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loc","family":"Le","sequence":"additional","affiliation":[{"name":"Bladder Immunology Group Biomedical Research Institute Rockville Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke F.","family":"Pennington","sequence":"additional","affiliation":[{"name":"Department of Structural Biology Stanford University School of Medicine Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin I.","family":"Odegaard","sequence":"additional","affiliation":[{"name":"OneOme Redwood City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore S.","family":"Jardetzky","sequence":"additional","affiliation":[{"name":"Department of Structural Biology Stanford University School of Medicine Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulaziz","family":"Alouffi","sequence":"additional","affiliation":[{"name":"Life Science and Environment Sector King Abdulaziz City for Science and Technology Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco H.","family":"Falcone","sequence":"additional","affiliation":[{"name":"Division of Molecular Therapeutics and Formulation School of Pharmacy University of Nottingham Nottingham United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael H.","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Bladder Immunology Group Biomedical Research Institute Rockville Maryland USA"},{"name":"Division of Urology Children's National Medical Center Washington District of Columbia USA"},{"name":"Department of Urology The George Washington University Washington District of Columbia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2255"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-006-0078-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyw093"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)36462-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1991.9.11.2016"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8588(18)30243-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000073350"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-006-0307-5"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2016.07.030"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-011-9319-3"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-010-1392-z"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etp.2007.10.010"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00240-003-0398-y"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)65134-8"},{"key":"e_1_2_8_16_1","first-page":"1103","article-title":"Participation of TNF\u2010alpha and IL\u20101 in the pathogenesis of cyclophosphamide\u2010induced hemorrhagic cystitis","volume":"28","author":"Gomes T. 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