Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media

• Published in: International journal of pediatric otorhinolaryngology Vol. 88; pp. 104 - 108
• Main Authors: Samuels, Tina L., Yan, Justin, Khampang, Pawjai, MacKinnon, Alexander, Hong, Wenzhou, Johnston, Nikki, Kerschner, Joseph E.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.09.2016
• Subjects: Cells, Cultured; Child; Child, Preschool; Ear, Middle - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Humans; Hyperplasia; In Vitro Techniques; Infant; Inflammation - pathology; Interleukin-1 Receptor-Associated Kinases - drug effects; Interleukin-1 Receptor-Associated Kinases - genetics; Interleukin-1beta - pharmacology; IRAK1; Male; MicroRNAs - drug effects; MicroRNAs - genetics; miR-146a; miR-146b; Otitis media; Otitis Media - genetics; Otitis Media - immunology; Otitis Media - pathology; Otitis Media - surgery; Otitis Media with Effusion - genetics; Otitis Media with Effusion - immunology; Otitis Media with Effusion - pathology; Otitis Media with Effusion - surgery; Otolaryngology; Pediatrics; Signal Transduction; TNF Receptor-Associated Factor 6 - drug effects; TNF Receptor-Associated Factor 6 - genetics; Toll-like receptor; Toll-Like Receptors; TRAF6; Tumor Necrosis Factor-alpha - pharmacology; Otitis media; miR-146a; miR-146b; IRAK1; TRAF6; Toll-like receptor; toll-like receptor; otitis media
• ISSN: 0165-5876; 1872-8464; 1872-8464
• DOI: 10.1016/j.ijporl.2016.06.056

Toll-like receptor signaling activated by bacterial otitis media pathogens in the middle ear has been shown to play a key role in OM susceptibility, pathogenesis and recovery. Recent studies implicate microRNA 146 (miR-146) in regulation of inflammation via negative feedback of toll-like receptor signaling (TLR) in a wide variety of tissues, however its involvement in otitis media is unknown. Human middle ear epithelial cells were stimulated with proinflammatory cytokines, interleukin 1 beta or tumor necrosis factor alpha, for two to twenty-four hours. Middle ear biopsies were collected from children with otitis media with effusion (n = 20), recurrent otitis media (n = 9), and control subjects undergoing cochlear implantation (n = 10). miR-146a, miR-146b expression was assayed by quantitative PCR (qPCR). Expression of miR-146 targets involved in TLR signaling, IRAK1 and TRAF6, was assayed by qPCR in middle ear biopsies. Middle ear biopsies were cryosectioned and epithelial thickness measured by a certified pathologist. Proinflammatory cytokines induced expression of miR-146 in middle ear epithelial cells in vitro. Middle ear miR-146a and miR-146b expression was elevated in otitis media patients relative to control subjects and correlated with middle ear epithelial thickness. A trend towards inverse correlation was observed between miR-146 and TRAF6 expression in the clinical population. This report is the first to assess miRNA expression in a clinical population with OM. Findings herein suggest miR-146 may play a role in OM.