{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:19:24Z","timestamp":1772626764604,"version":"3.50.1"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recurrent, rapidly growing nasal polyps are hallmarks of aspirin-exacerbated respiratory disease (AERD), although the mechanisms of polyp growth have not been identified. Fibroblasts are intimately involved in tissue remodeling, and the growth of fibroblasts is suppressed by prostaglandin E2 (PGE2), which elicits antiproliferative effects mediated through the E prostanoid (EP)2 receptor. We now report that cultured fibroblasts from the nasal polyps of subjects with AERD resist this antiproliferative effect. Fibroblasts from polyps of subjects with AERD resisted the antiproliferative actions of PGE2 and a selective EP2 agonist (P\u2009&amp;lt;\u20090.0001 at 1 \u03bcM) compared with nasal fibroblasts from aspirin-tolerant control subjects undergoing polypectomy or from healthy control subjects undergoing concha bullosa resections. Cell surface expression of the EP2 receptor protein was lower in fibroblasts from subjects with AERD than in fibroblasts from healthy control subjects and aspirin-tolerant subjects (P\u2009&amp;lt;\u20090.01 for both). Treatment of the fibroblasts with trichostatin A, a histone deacetylase inhibitor, significantly increased EP2 receptor mRNA in fibroblasts from AERD and aspirin-tolerant subjects but had no effect on cyclooxygenase-2, EP4, and microsomal PGE synthase 1 (mPGES-1) mRNA levels. Histone acetylation (H3K27ac) at the EP2 promoter correlated strongly with baseline EP2 mRNA (r\u2009=\u20090.80; P\u2009&amp;lt;\u20090.01). These studies suggest that the EP2 promotor is under epigenetic control, and one explanation for PGE2 resistance in AERD is an epigenetically mediated reduction of EP2 receptor expression, which could contribute to the refractory nasal polyposis typically observed in this syndrome.<\/jats:p>","DOI":"10.1165\/rcmb.2014-0486oc","type":"journal-article","created":{"date-parts":[[2015,6,6]],"date-time":"2015-06-06T14:20:32Z","timestamp":1433600432000},"page":"34-40","source":"Crossref","is-referenced-by-count":64,"title":["Impaired E Prostanoid2 Expression and Resistance to Prostaglandin E2 in Nasal Polyp Fibroblasts from Subjects with Aspirin-Exacerbated Respiratory Disease"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8549-1835","authenticated-orcid":false,"given":"Katherine N.","family":"Cahill","sequence":"first","affiliation":[{"name":"Departments of Medicine and"},{"name":"Division of Rheumatology, Immunology, and 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Massachusetts; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyang-Min","family":"Byun","sequence":"additional","affiliation":[{"name":"Harvard School of Public Health, Boston, Massachusetts; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Surgery, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Otology and Laryngology, Brigham and Women's Hospital, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W.","family":"Steinke","sequence":"additional","affiliation":[{"name":"Asthma and Allergic Disease Center, Carter Immunology Center, University of Virginia Health System, Charlottesville, Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua A.","family":"Boyce","sequence":"additional","affiliation":[{"name":"Departments of Medicine and"},{"name":"Division of Rheumatology, 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