{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T03:53:27Z","timestamp":1778039607952,"version":"3.51.4"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,3,5]],"date-time":"2014-03-05T00:00:00Z","timestamp":1393977600000},"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":[[2014,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sinonasal epithelial cells are recognized as drivers of inflammation in chronic sinusitis with nasal polyps (CRSwNP) through secretion of T helper 2 (Th2)\u2010promoting cytokines. P\u2010glycoprotein (P\u2010gp) is overexpressed in nasal polyps and modulates epithelial cytokine secretion in healthy mucosa. The objective of this study is to determine whether P\u2010gp overactivity promotes Th2\u2010associated cytokine secretion in CRSwNP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Polyp explants (n = 4) and primary epithelial cell cultures (n = 5) were cultivated from patients with CRSwNP. Explant P\u2010gp activity was determined using a calcein assay. In culture, P\u2010gp was quantified by enzyme\u2010linked immunosorbent assay (ELISA) and sensitivity to PSC\u2010833 inhibition was determined using a calcein assay. Lipopolysaccharide (LPS)\u2010stimulated cytokine secretion of interleukin 6 (IL\u20106), IL\u20108, IL\u201025, and granulocyte macrophage colony stimulating factor (GM\u2010CSF) were quantified by ELISA and compared to secretion following P\u2010gp inhibition. Differences in P\u2010gp expression and cytokine secretion were compared using a Mann\u2010Whitney <jats:italic>U<\/jats:italic> test. Secretion was correlated with P\u2010gp expression using a Pearson correlation coefficient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Calcein retention is increased in P\u2010gp inhibited vs uninhibited polyp explants (mean \u00b1 standard deviation [SD]; 5.17 \u00b1 1.76 vs 2.55 \u00b1 0.62; <jats:italic>p<\/jats:italic> &lt; 0.05) but not in controls, indicating increased nasal polyp P\u2010gp activity. P\u2010gp is sensitive to dose\u2010dependent P\u2010gp inhibition with PSC\u2010833 in vitro. LPS\u2010stimulated secretion of normalized GM\u2010CSF (45.21 \u00b1 41.39) and IL\u20106 (63.16 \u00b1 36.37) were significantly reduced following P\u2010gp inhibition (8.47 \u00b1 3.28; <jats:italic>p<\/jats:italic> &lt; 0.01, and 39.94 \u00b1 31.07; <jats:italic>p<\/jats:italic> &lt; 0.05; respectively) and secretion was highly correlated with P\u2010gp expression(<jats:italic>r<\/jats:italic> = 0.824, <jats:italic>p<\/jats:italic> &lt; 0.05, and <jats:italic>r<\/jats:italic> = 0.833, <jats:italic>p<\/jats:italic> &lt; 0.05; respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>P\u2010gp overactivity promotes Th2\u2010associated epithelial cytokine secretion in nasal polyps, suggesting a novel mechanism for maintaining chronic inflammation in CRSwNP.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.21316","type":"journal-article","created":{"date-parts":[[2014,3,5]],"date-time":"2014-03-05T16:17:55Z","timestamp":1394036275000},"page":"488-494","source":"Crossref","is-referenced-by-count":23,"title":["P\u2010glycoprotein promotes epithelial T helper 2\u2013associated cytokine secretion in chronic sinusitis with nasal polyps"],"prefix":"10.1002","volume":"4","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":"Angela L.","family":"Nocera","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hufsa","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"Hoang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulises","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel E.","family":"Feldman","sequence":"additional","affiliation":[{"name":"Massachusetts Eye and Ear Infirmary Harvard Medical School  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"}]}],"member":"311","published-online":{"date-parts":[[2014,3,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOO.0b013e32835bc3f9"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2010.02381.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2005.11.016"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21004"},{"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":"10.1177\/194589240602000203"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1398-9995.2002.02156.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.07.049"},{"key":"e_1_2_6_10_1","first-page":"145","article-title":"Eosinophilic nasal polyps are a rich source of eotaxin, eotaxin\u20102 and 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