{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:27:11Z","timestamp":1780493231837,"version":"3.54.1"},"reference-count":30,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Am J Rhinol\ufffdAllergy"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Methotrexate (MTX) is a very effective treatment for chronic inflammatory diseases that induces apoptosis in nasal polyps (NPs). However, the precise apoptotic pathway in NPs remains unclear. The aim of this study was to identify the apoptotic signaling pathways activated by MTX in NPs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>NP tissues were organ cultured using an air\u2013liquid interface method. Cultures were maintained in the presence or absence of MTX (10 or 100 \u03bcM) for 24 hours. To investigate apoptotic signaling in NPs, we performed reverse transcription\u2013polymerase chain reaction and Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MTX-treated NPs contained significantly increased amounts of the active forms of caspase 8, caspase 9, and caspase 3 and displayed increased cleavage of poly(ADP-ribose) polymerase. Expression of the proapoptotic molecules Bax and Bad at the mRNA and protein levels and of the activated molecules p-Bad and tBid was significantly higher in MTX-treated NPs than in nontreated NPs. In contrast, expression of the antiapoptotic molecule Bcl-2 at the mRNA and protein levels was significantly lower in MTX-treated NPs than in nontreated NPs. Expression of the phosphorylated forms of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) was significantly higher in MTX-treated NPs than in nontreated NPs. In contrast, expression of the phosphorylated form of Akt was significantly lower in MTX-treated NPs than in nontreated NPs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MTX induces apoptosis in NPs via caspase cascades and both mitochondria-mediated and p38 MAPK\/JNK pathways. We suggest that MTX can be used to treat NPs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2500\/ajra.2013.27.3849","type":"journal-article","created":{"date-parts":[[2013,2,9]],"date-time":"2013-02-09T15:39:15Z","timestamp":1360424355000},"page":"e26-e31","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Methotrexate Induces Apoptosis in Nasal Polyps\n                    <i>via<\/i>\n                    Caspase Cascades and Both Mitochondria-Mediated and p38 Mitogen-Activated Protein Kinases\/Jun N-terminal Kinase Pathways"],"prefix":"10.1177","volume":"27","author":[{"given":"Hong Wook","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery, Inje University, College of Medicine, Pusan Paik Hospital, Busan, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Kook","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery, Inje University, College of Medicine, Pusan Paik Hospital, Busan, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Wook","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery, Inje University, College of Medicine, Pusan Paik Hospital, Busan, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Young","family":"Hur","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Research Center for Tumor Immunology, Inje University, College of Medicine, Pusan Paik Hospital, Busan, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2013,1,1]]},"reference":[{"key":"bibr1-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.117819"},{"key":"bibr2-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1378\/chest.127.1.266"},{"key":"bibr3-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-004-0639-8"},{"key":"bibr4-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.12.6425"},{"key":"bibr5-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1177\/000348940010900306"},{"key":"bibr6-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00604-9"},{"key":"bibr7-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1126\/science.8235659"},{"key":"bibr8-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.41.26900"},{"key":"bibr9-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00338-7"},{"key":"bibr10-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20070"},{"key":"bibr11-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.01.071"},{"key":"bibr12-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2008.01745.x"},{"key":"bibr13-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1185\/03007990802643466"},{"key":"bibr14-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2012.26.3754"},{"key":"bibr15-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2011.25.3618"},{"key":"bibr16-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2006.09.014"},{"key":"bibr17-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.023408"},{"key":"bibr18-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2676"},{"key":"bibr19-ajra.2013.27.3849","doi-asserted-by":"crossref","first-page":"219","DOI":"10.2340\/00015555-0423","volume":"88","author":"Dahlman-Ghozlan K.","year":"2008","journal-title":"Acta Derm Venereol"},{"key":"bibr20-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5303.1132"},{"key":"bibr21-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.15.1.269"},{"key":"bibr22-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(00)00694-7"},{"key":"bibr23-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1139\/o97-043"},{"key":"bibr24-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.40.28379"},{"key":"bibr25-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200306000-00015"},{"key":"bibr26-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81004-1"},{"key":"bibr27-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.15.1899"},{"key":"bibr28-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1054\/drup.2001.0214"},{"key":"bibr29-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007147200"},{"key":"bibr30-ajra.2013.27.3849","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(01)01116-X"}],"container-title":["American Journal of Rhinology &amp; 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