Cytokine Levels in Inner Ear Fluid of Young and Aged Mice as Molecular Biomarkers of Noise-Induced Hearing Loss
Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide, frequently caused by noise trauma and aging, with inflammation being implicated in both pathologies. Here, we provide the first direct measurements of proinflammatory cytokines in inner ear fluid, perilymph, of adolescen...
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2019.00977/full |
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doaj-ba04d1af4058479ea31536f3591fe2eb2020-11-25T02:05:27ZengFrontiers Media S.A.Frontiers in Neurology1664-22952019-09-011010.3389/fneur.2019.00977485608Cytokine Levels in Inner Ear Fluid of Young and Aged Mice as Molecular Biomarkers of Noise-Induced Hearing LossLukas D. Landegger0Lukas D. Landegger1Lukas D. Landegger2Sasa Vasilijic3Sasa Vasilijic4Takeshi Fujita5Takeshi Fujita6Vitor Y. Soares7Vitor Y. Soares8Richard Seist9Richard Seist10Lei Xu11Konstantina M. Stankovic12Konstantina M. Stankovic13Konstantina M. Stankovic14Konstantina M. Stankovic15Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesDepartment of Otolaryngology, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaEaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesEaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesEaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesEaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesEdwin L. Steele Laboratories, Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United StatesEaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology—Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesProgram in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, MA, United StatesProgram in Therapeutic Science, Harvard Medical School, Boston, MA, United StatesSensorineural hearing loss (SNHL) is the most common sensory deficit worldwide, frequently caused by noise trauma and aging, with inflammation being implicated in both pathologies. Here, we provide the first direct measurements of proinflammatory cytokines in inner ear fluid, perilymph, of adolescent and 2-year-old mice. The perilymph of adolescent mice exposed to the noise intensity resulting in permanent auditory threshold elevations had significantly increased levels of IL-6, TNF-α, and CXCL1 6 h after exposure, with CXCL1 levels being most elevated (19.3 ± 6.2 fold). We next provide the first immunohistochemical localization of CXCL1 in specific cochlear supporting cells, and its presumed receptor, Duffy antigen receptor for chemokines (DARC), in hair cells and spiral ganglion neurons. Our results demonstrate the feasibility of molecular diagnostics of SNHL using only 0.5 μL of perilymph, and motivate future sub-μL based diagnostics of human SNHL based on liquid biopsy of the inner ear to guide therapy, promote hearing protection, and monitor response to treatment.https://www.frontiersin.org/article/10.3389/fneur.2019.00977/fullperilymphnoise-induced hearing losscytokinesCXCL1DARCage-related hearing loss |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Lukas D. Landegger Lukas D. Landegger Lukas D. Landegger Sasa Vasilijic Sasa Vasilijic Takeshi Fujita Takeshi Fujita Vitor Y. Soares Vitor Y. Soares Richard Seist Richard Seist Lei Xu Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic |
| spellingShingle |
Lukas D. Landegger Lukas D. Landegger Lukas D. Landegger Sasa Vasilijic Sasa Vasilijic Takeshi Fujita Takeshi Fujita Vitor Y. Soares Vitor Y. Soares Richard Seist Richard Seist Lei Xu Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic Cytokine Levels in Inner Ear Fluid of Young and Aged Mice as Molecular Biomarkers of Noise-Induced Hearing Loss Frontiers in Neurology perilymph noise-induced hearing loss cytokines CXCL1 DARC age-related hearing loss |
| author_facet |
Lukas D. Landegger Lukas D. Landegger Lukas D. Landegger Sasa Vasilijic Sasa Vasilijic Takeshi Fujita Takeshi Fujita Vitor Y. Soares Vitor Y. Soares Richard Seist Richard Seist Lei Xu Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic Konstantina M. Stankovic |
| author_sort |
Lukas D. Landegger |
| title |
Cytokine Levels in Inner Ear Fluid of Young and Aged Mice as Molecular Biomarkers of Noise-Induced Hearing Loss |
| title_short |
Cytokine Levels in Inner Ear Fluid of Young and Aged Mice as Molecular Biomarkers of Noise-Induced Hearing Loss |
| title_full |
Cytokine Levels in Inner Ear Fluid of Young and Aged Mice as Molecular Biomarkers of Noise-Induced Hearing Loss |
| title_fullStr |
Cytokine Levels in Inner Ear Fluid of Young and Aged Mice as Molecular Biomarkers of Noise-Induced Hearing Loss |
| title_full_unstemmed |
Cytokine Levels in Inner Ear Fluid of Young and Aged Mice as Molecular Biomarkers of Noise-Induced Hearing Loss |
| title_sort |
cytokine levels in inner ear fluid of young and aged mice as molecular biomarkers of noise-induced hearing loss |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Neurology |
| issn |
1664-2295 |
| publishDate |
2019-09-01 |
| description |
Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide, frequently caused by noise trauma and aging, with inflammation being implicated in both pathologies. Here, we provide the first direct measurements of proinflammatory cytokines in inner ear fluid, perilymph, of adolescent and 2-year-old mice. The perilymph of adolescent mice exposed to the noise intensity resulting in permanent auditory threshold elevations had significantly increased levels of IL-6, TNF-α, and CXCL1 6 h after exposure, with CXCL1 levels being most elevated (19.3 ± 6.2 fold). We next provide the first immunohistochemical localization of CXCL1 in specific cochlear supporting cells, and its presumed receptor, Duffy antigen receptor for chemokines (DARC), in hair cells and spiral ganglion neurons. Our results demonstrate the feasibility of molecular diagnostics of SNHL using only 0.5 μL of perilymph, and motivate future sub-μL based diagnostics of human SNHL based on liquid biopsy of the inner ear to guide therapy, promote hearing protection, and monitor response to treatment. |
| topic |
perilymph noise-induced hearing loss cytokines CXCL1 DARC age-related hearing loss |
| url |
https://www.frontiersin.org/article/10.3389/fneur.2019.00977/full |
| work_keys_str_mv |
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