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 Steyger

Research output: Contribution to journalArticle

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

Fingerprint

auditory defects
drugs
hair
infectious diseases
knockout mice
antibiotics
polymorphism
cells
stimulation
membranes
cations
thresholds

ASJC Scopus subject areas

  • General
  • Physics and Astronomy (miscellaneous)

Cite this

Inflammation up-regulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss. / Jiang, Meiyan; Li, Hongzhe; Johnson, Anastasiya; Karasawa, Takatoshi; Zhang, Yuan; Meier, William B.; Taghizadeh, Farshid; Kachelmeier, Allan; Steyger, Peter.

In: Science Advances, Vol. 5, No. 7, eaaw1836, 17.07.2019.

Research output: Contribution to journalArticle

Jiang, M, Li, H, Johnson, A, Karasawa, T, Zhang, Y, Meier, WB, Taghizadeh, F, Kachelmeier, A & Steyger, P 2019, 'Inflammation up-regulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss', Science Advances, vol. 5, no. 7, eaaw1836. https://doi.org/10.1126/sciadv.aaw1836
Jiang, Meiyan ; Li, Hongzhe ; Johnson, Anastasiya ; Karasawa, Takatoshi ; Zhang, Yuan ; Meier, William B. ; Taghizadeh, Farshid ; Kachelmeier, Allan ; Steyger, Peter. / Inflammation up-regulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss. In: Science Advances. 2019 ; Vol. 5, No. 7.
@article{7ffea62e9f70413aab8261097f50b66a,
title = "Inflammation up-regulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss",
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.",
author = "Meiyan Jiang and Hongzhe Li and Anastasiya Johnson and Takatoshi Karasawa and Yuan Zhang and Meier, {William B.} and Farshid Taghizadeh and Allan Kachelmeier and Peter Steyger",
year = "2019",
month = "7",
day = "17",
doi = "10.1126/sciadv.aaw1836",
language = "English (US)",
volume = "5",
journal = "Indian Journal of Pure and Applied Physics",
issn = "0019-5596",
publisher = "National Institute of Science Communication and Information Resources (NISCAIR)",
number = "7",

}

TY - JOUR

T1 - Inflammation up-regulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss

AU - Jiang, Meiyan

AU - Li, Hongzhe

AU - Johnson, Anastasiya

AU - Karasawa, Takatoshi

AU - Zhang, Yuan

AU - Meier, William B.

AU - Taghizadeh, Farshid

AU - Kachelmeier, Allan

AU - Steyger, Peter

PY - 2019/7/17

Y1 - 2019/7/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85069943286&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069943286&partnerID=8YFLogxK

U2 - 10.1126/sciadv.aaw1836

DO - 10.1126/sciadv.aaw1836

M3 - Article

VL - 5

JO - Indian Journal of Pure and Applied Physics

JF - Indian Journal of Pure and Applied Physics

SN - 0019-5596

IS - 7

M1 - eaaw1836

ER -