Inflammation up-regulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss

Meiyan Jiang, Hongzhe Li, Anastasiya Johnson, Takatoshi Karasawa, Yuan Zhang, William B. Meier, Farshid Taghizadeh, Allan Kachelmeier, Peter S. Steyger

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Aminoglycoside antibiotics are essential for treating life-threatening bacterial infections, despite the risk of lifelong hearing loss. Infections induce inflammation and up-regulate expression of candidate aminoglycoside-permeant cation channels, including transient receptor potential vanilloid-1 (TRPV1). Heterologous expression of TRPV1 facilitated cellular uptake of (fluorescently tagged) gentamicin that was enhanced by agonists, and diminished by antagonists, of TRPV1. Cochlear TRPV1 was immunolocalized near the apical membranes of sensory hair cells, adjacent supporting cells, and marginal cells in the stria vascularis. Exposure to immunostimulatory lipopolysaccharides, to simulate of bacterial infections, increased cochlear expression of TRPV1 and hair cell uptake of gentamicin. Lipopolysaccharide exposure exacerbated aminoglycoside-induced auditory threshold shifts and loss of cochlear hair cells in wild-type, but not in heterozygous Trpv1+/− or Trpv1 knockout, mice. Thus, TRPV1 facilitates cochlear uptake of aminoglycosides, and bacteriogenic stimulation upregulates TRPV1 expression to exacerbate cochleotoxicity. Furthermore, loss-of-function polymorphisms in Trpv1 can protect against immuno-genic exacerbation of aminoglycoside-induced cochleotoxicity.

Original languageEnglish (US)
Article numbereaaw1836
JournalScience Advances
Volume5
Issue number7
DOIs
StatePublished - Jul 17 2019

ASJC Scopus subject areas

  • Physics and Astronomy (miscellaneous)
  • General

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    Jiang, M., Li, H., Johnson, A., Karasawa, T., Zhang, Y., Meier, W. B., Taghizadeh, F., Kachelmeier, A., & Steyger, P. S. (2019). Inflammation up-regulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss. Science Advances, 5(7), [eaaw1836]. https://doi.org/10.1126/sciadv.aaw1836