Altered expression of middle and inner ear cytokines in mouse otitis media

Authors

  • Carol J. MacArthur MD,

    Corresponding author
    1. Department of Otolaryngology, Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon, U.S.A.
    • Associate Professor, Department of Otolaryngology, Head and Neck Surgery, Oregon Health and Science University, 3181 SW Sam Jackson University, PV-01, Portland, OR 97239-3098
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  • De-Ann M. Pillers MD, PhD,

    1. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, Portland, Oregon, U.S.A.
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  • Jiaqing Pang MS,

    1. Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon, U.S.A
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  • J. Beth Kempton BS,

    1. Department of Otolaryngology, Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon, U.S.A.
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  • Dennis R. Trune PhD

    1. Department of Otolaryngology, Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon, U.S.A.
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  • Presented at Association for Research in Otolaryngology Meeting, Phoenix, Arizona, U.S.A., February 6–10, 2008.

  • Supported by NIH NIDCD R01 DC 09455 and NIDCD P30 DC005983. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis:

The inner ear is at risk for sensorineural hearing loss in both acute and chronic otitis media (OM), but the mechanisms underlying sensorineural hearing loss are unknown. Previous gene expression array studies have shown that cytokine genes might be upregulated in the cochleas of mice with acute and chronic OM. This finding implies that the inner ear could manifest a direct inflammatory response to OM that may cause sensorineural damage. Therefore, to better understand inner ear cytokine gene expression during OM, quantitative real-time polymerase chain reaction and immunohistochemistry were used in mouse models to evaluate middle and inner ear inflammatory and remodeling cytokines.

Study Design:

Basic science experiment.

Methods:

An acute OM model was created in Balb/c mice by a transtympanic injection of Streptococcuspneumoniae in one ear; the other ear was used as a control. C3H/HeJ mice were screened for unilateral chronic OM, with the noninfected ear serving as a control.

Results:

Both acute and chronic OM caused both the middle ear and inner tissues in these two mouse models to overexpress numerous cytokine genes related to tissue remodeling (tumor necrosis factor-α, bone morphogenetic proteins, fibroblast growth factors) and angiogenesis (vascular endothelial growth factor), as well as inflammatory cell proliferation (interleukin [IL]-1α,β, IL-2, IL-6). Immunohistochemistry confirmed that both the middle ear and inner ear tissues expressed these cytokines.

Conclusions:

Cochlear tissues are capable of expressing cytokine mRNA that contributes to the inflammation and remodeling that occur in association with middle ear disease. This provides a potential molecular basis for the transient and permanent sensorineural hearing loss often reported with acute and chronic OM.

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