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Published on: January 4, 2017
Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media
Tina L Samuels1, Justin Yan1, Pawjai Khampang1
1Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA.
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.
Insights
MicroRNA 146 (miR-146) expression is elevated in middle ear tissues of otitis media patients. This suggests miR-146 plays a role in the inflammatory processes of otitis media.
Area of Science:
- Immunology
- Molecular Biology
- Otolaryngology
Background:
- Toll-like receptor (TLR) signaling is crucial in otitis media (OM) pathogenesis.
- MicroRNA 146 (miR-146) is known to regulate inflammation via negative feedback of TLR signaling in various tissues.
- The role of miR-146 in otitis media remains unexplored.
Purpose of the Study:
- To investigate the expression and role of miR-146 in human otitis media.
- To determine if miR-146 is differentially expressed in middle ear tissues of OM patients compared to controls.
Main Methods:
- Human middle ear epithelial cells were stimulated with pro-inflammatory cytokines in vitro.
- Middle ear biopsies from patients with otitis media (effusion and recurrent) and controls were analyzed.
- Quantitative PCR (qPCR) was used to measure miR-146a, miR-146b, and their target gene (IRAK1, TRAF6) expression.
- Epithelial thickness was measured in biopsy cryosections.
Main Results:
- Pro-inflammatory cytokines induced miR-146 expression in middle ear epithelial cells.
- miR-146a and miR-146b expression were significantly elevated in middle ear biopsies from OM patients.
- Elevated miR-146 expression correlated with increased middle ear epithelial thickness.
- A trend towards inverse correlation between miR-146 and TRAF6 expression was observed.
Conclusions:
- This study is the first to examine miRNA expression in a clinical population with otitis media.
- Findings suggest that miR-146 plays a significant role in the pathogenesis of otitis media.
- miR-146 may serve as a potential biomarker or therapeutic target for otitis media.

