{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T16:32:25Z","timestamp":1715704345074},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102017R1C1B5076754"],"award-info":[{"award-number":["NRF\u20102017R1C1B5076754"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Oral steroids are recommended for the treatment of nasal polyps (NPs), but prolonged use is avoided because of side effects. Topical steroids can also control NPs without significant complications; however, the response to this is partially successful, and additional therapies are needed to treat glucocorticoid\u2010resistant NPs. Azathioprine (AZA) and its first metabolite 6\u2010mercaptopurine (6\u2010MP) are important immunosuppressants used for the therapy of various diseases. The aim of this study was to investigate the effects of AZA and 6\u2010MP on inflammatory cytokines in organ\u2010cultured NPs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>NP explants were cultured using an air\u2010liquid interface method. Cultures were maintained in the absence and presence of steroid, AZA, and 6\u2010MP for 72 hours. Elaboration of cytokines tumor necrosis factor alpha (TNF\u2010\u03b1), interleukin (IL)\u20102, IL\u20104, IL\u20105, and IL\u201013 into the supernatant was quantitated using the enzyme\u2010linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expression levels of TNF\u2010\u03b1, IL\u20102, IL\u20104, IL\u20105, and IL\u201013 in cultured mucosa were measured using real\u2010time polymerase chain reaction. Hematoxylin and eosin staining of cultured mucosa was performed to observe inflammatory cells. Immunohistochemistry was done to evaluate the distribution pattern of inflammatory cytokines in NP explants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>On histologic examination, less inflammatory cell infiltration was found in NPs treated by steroid, AZA, and 6\u2010MP than in control, but there was no statistical significance (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.218). On immunohistochemistry, IL\u201013 showed a steady falling tendency in submucosal glands by steroid, AZA, and 6\u2010MP. Expression of TNF\u2010\u03b1, IL\u20102, IL\u20104, IL\u20105, and IL\u201013 mRNA in the NPs treated by steroid, AZA, and 6\u2010MP were significantly lower than those of the control (<jats:italic>p\u00a0&lt;\u00a0<\/jats:italic>0.001 for all). By ELISA, IL\u20102 and IL\u201013 were significantly lower with topical steroid, AZA, and 6\u2010MP treatment (<jats:italic>p\u00a0=\u00a0<\/jats:italic>0.012 and <jats:italic>p\u00a0&lt;\u00a0<\/jats:italic>0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Topical AZT decreases inflammatory cytokines on human NP explants and this could have future therapeutic implications for NPs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22303","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T17:06:11Z","timestamp":1549991171000},"page":"648-655","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of azathioprine and its metabolites on inflammatory cytokines in human nasal polyp organ cultures"],"prefix":"10.1002","volume":"9","author":[{"given":"Nam\u2010Kyung","family":"Yeo","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, 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