{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T13:12:18Z","timestamp":1770469938369,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"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":[[2016,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>T\u2010helper 2 (Th2) inflammation is a hallmark of chronic rhinosinusitis with nasal polyps (CRSwNP) although the pathogenesis is poorly understood. P\u2010glycoprotein (permeability glycoprotein, P\u2010gp) is an efflux pump that is capable of regulating cytokine transport and is expressed within sinonasal mucosa. The purpose of this study was to examine if the oversecretion of interleukin 5 (IL\u20105) and thymic stromal lymphopoietin (TSLP) in CRSwNP could be explained through P\u2010gp\u2013mediated secretory pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifteen ethmoid mucosal explants were harvested from patients with CRS (n = 10) and CRSwNP (n = 10) and stimulated with <jats:italic>Staphylococcus aureus<\/jats:italic> enterotoxin B (SEB). P\u2010gp was inhibited using zosuquidar trihydrochloride (herein Zosuquidar). P\u2010gp expression was measured using real\u2010time polymerase chain reaction (RT\u2010PCR) and enzyme\u2010linked immunosorbent assay (ELISA). IL\u20105, IL\u20108, and TSLP secretion were quantified using ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>P\u2010gp protein was overexpressed in CRSwNP (28.32 \u00b1 25.94 ng\/mL per mg explant) as compared to CRS (10.74 \u00b1 8.61; <jats:italic>p<\/jats:italic> = 0.01, 2\u2010tailed Mann\u2010Whitney <jats:italic>U<\/jats:italic> test). There was no difference in messenger RNA (mRNA) expression. SEB induced a significant increase in IL\u20105 and TSLP but not IL\u20108 secretion relative to control in the CRSwNP explants only. Subsequent P\u2010gp inhibition significantly reduced IL\u20105 and TSLP secretion (<jats:italic>p<\/jats:italic> = 0.04 for both, 2\u2010tailed Student <jats:italic>t<\/jats:italic> test) to control levels. The concentration of IL\u20105 and TSLP secretion were strongly and significantly correlated to the concentration of P\u2010gp within the same explant (IL\u20105: <jats:italic>r<\/jats:italic> = 0.791, <jats:italic>p<\/jats:italic> = 0.001; TSLP: <jats:italic>r<\/jats:italic> = 0.687, <jats:italic>p<\/jats:italic> = 0.003; 2\u2010tailed Spearman's rank\u2010order correlation).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>P\u2010gp protein is expressed at higher concentrations in CRSwNP as compared to CRS. This overexpression directly contributes to the relative hypersecretion of IL\u20105 and TSLP. These findings suggest a novel mechanism for Th2 skewing in CRSwNP.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.21566","type":"journal-article","created":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T16:30:50Z","timestamp":1448987450000},"page":"169-177","source":"Crossref","is-referenced-by-count":19,"title":["P\u2010glycoprotein regulates <i>Staphylococcus aureus<\/i> enterotoxin B\u2013stimulated interleukin\u20105 and thymic stromal lymphopoietin secretion in organotypic mucosal explants"],"prefix":"10.1002","volume":"6","author":[{"given":"Benjamin S.","family":"Bleier","sequence":"first","affiliation":[{"name":"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":"Angela 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