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Role of cysteinyl leukotriene signaling in a mouse model of noise-induced cochlear injury.

Authors
Park, JS; Kang, SJ; Seo, MK; Jou, I; Woo, HG; Park, SM
Citation
Proceedings of the National Academy of Sciences of the United States of America, 111(27):9911-9916, 2014
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-84241091-6490
Abstract
Noise-induced hearing loss is one of the most common types of sensorineural hearing loss. In this study, we examined the expression and localization of leukotriene receptors and their respective changes in the cochlea after hazardous noise exposure. We found that the expression of cysteinyl leukotriene type 1 receptor (CysLTR1) was increased until 3 d after noise exposure and enhanced CysLTR1 expression was mainly observed in the spiral ligament and the organ of Corti. Expression of 5-lipoxygenase was increased similar to that of CysLTR1, and there was an accompanying elevation of CysLT concentration. Posttreatment with leukotriene receptor antagonist (LTRA), montelukast, for 4 consecutive days after noise exposure significantly decreased the permanent threshold shift and also reduced the hair cell death in the cochlea. Using RNA-sequencing, we found that the expression of matrix metalloproteinase-3 (MMP-3) was up-regulated after noise exposure, and it was significantly inhibited by montelukast. Posttreatment with a MMP-3 inhibitor also protected the hair cells and reduced the permanent threshold shift. These findings suggest that acoustic injury up-regulated CysLT signaling in the cochlea and cochlear injury could be attenuated by LTRA through regulation of MMP-3 expression. This study provides mechanistic insights into the role of CysLTs signaling in noise-induced hearing loss and the therapeutic benefit of LTRA.
MeSH terms
Acetates/therapeutic useAnimalsCochlea/injuriesCysteine/metabolismDisease Models, AnimalGene Expression ProfilingLeukotriene Antagonists/therapeutic useLeukotrienes/metabolismMatrix Metalloproteinase 3/metabolismMiceNoise/adverse effectsQuinolines/therapeutic useReceptors, Leukotriene/drug effectsSignal TransductionWounds and Injuries/drug therapyWounds and Injuries/etiology
DOI
10.1073/pnas.1402261111
PMID
24958862
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
주, 일로우, 현구박, 상면
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