{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:09:09Z","timestamp":1760242149033,"version":"build-2065373602"},"reference-count":65,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T00:00:00Z","timestamp":1708732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>17\u03b2\u2010estradiol (E2) is a steroidal hormone with immunomodulatory functions that play a role in infectious and inflammatory diseases. E2 was recently identified as the leading upstream regulator of differentially expressed genes in a comparative RNA sequencing study of pediatric patients with otitis media (OM) versus OM\u2010free counterparts and may therefore play a role in the inflammatory response to bacterial otopathogens during pediatric OM. This study examined the effect of E2 on bacterial\u2010induced inflammatory cytokine expression in an <jats:italic>in vitro<\/jats:italic> pediatric OM model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An immortalized middle ear (ME) epithelial cell line, ROM\u2010SV40, was developed from a pediatric recurrent OM patient. The culture was exposed to E2 at physiological levels for 1\u201348\u2009h prior to 6\u2009h\u2010stimulation with nontypeable <jats:italic>Haemophilus influenzae<\/jats:italic> (NTHi) whole cell lysate. <jats:italic>TNFA<\/jats:italic>, <jats:italic>IL1B<\/jats:italic>, <jats:italic>IL6<\/jats:italic>, and <jats:italic>IL8<\/jats:italic> were assayed by qPCR and ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>E2 pretreatment (24\u2009h) abrogated NTHi induction of <jats:italic>IL6<\/jats:italic>; a longer pretreatment (1\u201310\u2009nM, 48\u2009h) abrogated <jats:italic>IL1B<\/jats:italic> induction (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). E2 pretreatment (5\u2009nM, 48\u2009h) abrogated NTHi\u2010induced IL8 secretion (<jats:italic>p<\/jats:italic>\u2009=\u20090.017).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>E2 pretreatment partially rescued NTHi\u2010induced cytokine production by ME epithelia. These data support a role for E2 in moderating the excessive inflammatory response to middle ear infection that contributes to OM pathophysiology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Levels of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 134:3815\u20133819, 2024<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.31343","type":"journal-article","created":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T12:05:00Z","timestamp":1708776300000},"page":"3815-3819","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["17\u03b2\u2010estradiol Attenuates the Middle Ear Inflammatory Response to Nontypeable <i>Haemophilus influenzae<\/i>"],"prefix":"10.1002","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8110-9758","authenticated-orcid":false,"given":"Pawjai","family":"Khampang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7045-357X","authenticated-orcid":false,"given":"Tina L.","family":"Samuels","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6027-1409","authenticated-orcid":false,"given":"Simon","family":"Blaine\u2010Sauer","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julliette","family":"Lucas","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Quantitative Health Sciences Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikki","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."},{"name":"Department of Microbiology and Immunology Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1813-7243","authenticated-orcid":false,"given":"Joseph E.","family":"Kerschner","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."},{"name":"Department of Microbiology and Immunology Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."},{"name":"Children's Wisconsin  Milwaukee Wisconsin U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2017-0181"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12913-023-09244-7"},{"key":"e_1_2_6_4_1","first-page":"8","article-title":"Recent advances in otitis media. 1. 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