title: Role of cysteinyl leukotriene signaling in a mouse model of noise-induced cochlear injury.
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.
authors: Department of Pharmacology,Department of Otolaryngology,Neuroscience Graduate Program, Department of Biological Sciences,Chronic Inflammatory Disease Research Center, and.
authors: Jung-Sub
authors: JS
authors: Park
authors: Department of Pharmacology,Neuroscience Graduate Program, Department of Biological Sciences,Chronic Inflammatory Disease Research Center, and.
authors: Seo-Jun
authors: SJ
authors: Kang
authors: Chronic Inflammatory Disease Research Center, andDepartment of Physiology, Ajou University School of Medicine, Yeongtong-gu, Suwon 443-380, Korea.
authors: Mi-Kyoung
authors: MK
authors: Seo
authors: Department of Pharmacology,Neuroscience Graduate Program, Department of Biological Sciences,Chronic Inflammatory Disease Research Center, and.
authors: Ilo
authors: I
authors: Jou
authors: Chronic Inflammatory Disease Research Center, andDepartment of Physiology, Ajou University School of Medicine, Yeongtong-gu, Suwon 443-380, Korea.
authors: Hyun Goo
authors: HG
authors: Woo
authors: Department of Pharmacology,Neuroscience Graduate Program, Department of Biological Sciences,Chronic Inflammatory Disease Research Center, and sangmyun@ajou.ac.kr.
authors: Sang Myun
authors: SM
authors: Park
mesh_terms: D000085:Acetates / Q000627:therapeutic use; D000818:Animals; D003051:Cochlea / Q000293:injuries*; D003521:Cyclopropanes; D003545:Cysteine / Q000378:metabolism*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D015289:Leukotrienes / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D051379:Mice; D009622:Noise / Q000009:adverse effects*; D011804:Quinolines / Q000627:therapeutic use; D018077:Receptors, Leukotriene / Q000187:drug effects; D015398:Signal Transduction; D013440:Sulfides; D014947:Wounds and Injuries / Q000188:drug therapy / Q000209:etiology
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; C112381:cysteinyl-leukotriene; D019278:Matrix Metalloproteinase 3; D003545:Cysteine; C083169:leukotriene D4 receptor; C093875:montelukast