{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T23:02:48Z","timestamp":1779318168924,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,8,22]],"date-time":"2014-08-22T00:00:00Z","timestamp":1408665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>P\u2010glycoprotein (P\u2010gp) is an efflux pump, which is part of the innate chemo\u2010immunity defense system and is overexpressed in chronic rhinosinusitis with nasal polyps (CRSwNP). P\u2010gp is capable of regulating corticosteroid retention and thus P\u2010gp upregulation has been implicated in steroid resistance in several inflammatory disorders. The goal of this study is to determine whether P\u2010gp regulates intracellular steroid retention in CRSwNP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a Massachusetts Eye and Ear Infirmary Institutional Review Board (IRB)\u2010approved study in nasal polyp explants. Polyps were exposed to 50 \u03bcg\/mL of prednisone for 30 minutes with or without the presence of a P\u2010gp inhibitor (Verapamil 12.5 \u03bcM or Zosuquidar 0.31 \u03bcM) followed by a 40\u2010minute washout period (n = 16 per group). Intracellular steroid retention was determined by quantifying the concentration of both intracytoplasmic and secreted steroid using an enzyme\u2010linked immunosorbent assay (ELISA). Concentrations relative to control were compared using a Student <jats:italic>t<\/jats:italic> test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The intracytoplasmic prednisone concentration was significantly greater relative to control following P\u2010gp inhibition with Verapamil (155.28% \u00b1 22.48%, <jats:italic>p<\/jats:italic> &lt; 0.05) and Zosuquidar (125.81% \u00b1 12.41%, <jats:italic>p<\/jats:italic> &lt; 0.05). Similarly, the amount of prednisone secreted by the explant was significantly reduced at 30 minutes following P\u2010gp inhibition with Zosuquidar (78.64% \u00b1 2.98%, <jats:italic>p<\/jats:italic> &lt; 0.05) and 40 minutes following P\u2010gp inhibition with Verapamil (80.56% \u00b1 5.02%, <jats:italic>p<\/jats:italic> &lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Inhibition of P\u2010gp enhances the intracellular accumulation of prednisone in nasal polyps. This suggests that P\u2010gp participates in regulation of glucocorticoid retention in sinonasal mucosa. These findings, coupled with the known overexpression of P\u2010gp in CRSwNP, may point to a possible mechanism for steroid resistance in this patient population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.21361","type":"journal-article","created":{"date-parts":[[2014,8,22]],"date-time":"2014-08-22T12:05:13Z","timestamp":1408709113000},"page":"734-738","source":"Crossref","is-referenced-by-count":16,"title":["P\u2010glycoprotein inhibition promotes prednisone retention in human sinonasal polyp explants"],"prefix":"10.1002","volume":"4","author":[{"given":"Armine","family":"Kocharyan","sequence":"first","affiliation":[{"name":"Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary Harvard Medical School  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary Harvard Medical School  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Singleton","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin S.","family":"Bleier","sequence":"additional","affiliation":[{"name":"Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary Harvard Medical School  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,8,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21004"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706992"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2500\/105065897781446603"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21176"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21166"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00491.2007"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01663-9"},{"issue":"23","key":"e_1_2_6_9_1","first-page":"3","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2012","author":"Fokkens WJ","year":"2012","journal-title":"Rhinol Suppl"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2005.04.006"},{"key":"e_1_2_6_11_1","first-page":"359","article-title":"Influence of the pro\u2010inflammatory cytokines on P\u2010glycoprotein expression and functionality","volume":"7","author":"Fernandez C","year":"2004","journal-title":"J Pharm Pharm Sci"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1360704"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi952380k"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"24248","DOI":"10.1016\/S0021-9258(18)35757-0","article-title":"Human P\u2010glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone","volume":"267","author":"Ueda K","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(02)00227-3"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2009.02.027"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70210-1"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200342010-00003"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-200X.2008.02541.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008212"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.294.5548.1866"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.21.12208"}],"container-title":["International Forum of Allergy &amp; 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