title: Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Tina L
authors: TL
authors: Samuels
authors: Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Justin
authors: J
authors: Yan
authors: Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Pawjai
authors: P
authors: Khampang
authors: Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Alexander
authors: A
authors: MacKinnon
authors: Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Wenzhou
authors: W
authors: Hong
authors: Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Nikki
authors: N
authors: Johnston
authors: Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: jkerschner@mcw.edu.
authors: Joseph E
authors: JE
authors: Kerschner
mesh_terms: D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004432:Ear, Middle / Q000166:cytology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D066298:In Vitro Techniques; D007223:Infant; D007249:Inflammation / Q000473:pathology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000187:drug effects / Q000235:genetics; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D035683:MicroRNAs / Q000187:drug effects* / Q000235:genetics; D010033:Otitis Media / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D010034:Otitis Media with Effusion / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000601:surgery; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000187:drug effects* / Q000235:genetics; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D053583:Interleukin-1beta; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D048029:TNF Receptor-Associated Factor 6; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: IRAK1; Otitis media; TRAF6; Toll-like receptor; miR-146a; miR-146b