{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:44:52Z","timestamp":1788975892075,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Institutes of Health Institute on Deafness and Communication Disorders","award":["5R21DC015634-02"],"award-info":[{"award-number":["5R21DC015634-02"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>Cell culture models are valuable tools for investigation of the molecular pathogenesis of diseases including otitis media (OM). Previous study indicates that age\u2010, sex\u2010, and race\u2010associated differences in molecular signaling may impact disease pathophysiology. Currently, a singular immortalized middle ear epithelial (MEE) cell line exists, HMEEC\u20101, derived from an adult without known middle ear disease. In this study, HMEEC\u20101 and primary MEE cultures from pediatric patients with and without OM were stimulated with inflammatory cytokines or OM\u2010pathogenic bacterial lysates to examine differences in the response of molecules associated with OM pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Case\u2013control series.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MEE cultures were established from patients aged &lt;6\u2009years: two with recurrent OM (ROM), two with OM with effusion (OME), and one patient without OM who was undergoing cochlear implant surgery control undergoing cochlear implantation (Peds CI). Primary MEE cultures and HMEEC\u20101 cells were stimulated with tumor necrosis factor\u2010\u03b1, interleukin (IL)\u20101\u03b2, or nontypeable <jats:italic>Haemophilus influenzae<\/jats:italic> lysate. <jats:italic>TNFA, IL1B, IL6, IL8, IL10<\/jats:italic>, and <jats:italic>MUC5B<\/jats:italic> were assayed via quantitative polymerase chain reaction. IL\u20108 was assayed by enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gene\/protein target expressions were frequently higher in pediatric OM lines than in HMEEC\u20101 and Peds CI. HMEEC\u20101 cells were frequently less responsive to stimuli than all pediatric lines. OME lines were often more responsive than ROM lines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>OM may be associated with specific molecular phenotypes that are retained in primary cell culture. Adult\u2010derived HMEEC\u20101 cells differ significantly in baseline expression and response of OM\u2010associated molecules relative to pediatric MEE cells. Work is underway to immortalize pediatric OM MEE cultures as improved tools for the OM research community.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>4 <jats:italic>Laryngoscope<\/jats:italic>, 131:410\u2013416, 2021<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.28687","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T19:50:03Z","timestamp":1590004203000},"page":"410-416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Analysis of Inflammatory Signaling in Human Middle Ear Cell Culture Models of Pediatric Otitis Media"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2822-778X","authenticated-orcid":false,"given":"Mana","family":"Espahbodi","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Medical College of Wisconsin  Milwaukee Wisconsin 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Wisconsin U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7900-4896","authenticated-orcid":false,"given":"Michael E.","family":"McCormick","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Medical College of Wisconsin  Milwaukee Wisconsin U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Medical College of Wisconsin  Milwaukee 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