Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss.

Epidemiological data suggest that inflammation and innate immunity play significant roles in the pathogenesis of age-related hearing loss (ARHL) in humans. In this mouse study, real-time RT-PCR array targeting 84 immune-related genes revealed that the expressions of 40 genes (47.6%) were differentia...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Kensuke Uraguchi, Yukihide Maeda, Junko Takahara, Ryotaro Omichi, Shohei Fujimoto, Shin Kariya, Kazunori Nishizaki, Mizuo Ando
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/22742bdcaa764614b741cc24671168b6
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:22742bdcaa764614b741cc24671168b6
record_format dspace
spelling oai:doaj.org-article:22742bdcaa764614b741cc24671168b62021-12-02T20:13:33ZUpregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss.1932-620310.1371/journal.pone.0258977https://doaj.org/article/22742bdcaa764614b741cc24671168b62021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258977https://doaj.org/toc/1932-6203Epidemiological data suggest that inflammation and innate immunity play significant roles in the pathogenesis of age-related hearing loss (ARHL) in humans. In this mouse study, real-time RT-PCR array targeting 84 immune-related genes revealed that the expressions of 40 genes (47.6%) were differentially regulated with greater than a twofold change in 12-month-old cochleae with ARHL relative to young control mice, 33 (39.3%) of which were upregulated. These differentially regulated genes (DEGs) were involved in functional pathways for cytokine-cytokine receptor interaction, chemokine signaling, TNF signaling, and Toll-like receptor signaling. An NF-κB subunit, Nfkb1, was upregulated in aged cochleae, and bioinformatic analyses predicted that NF-κB would interact with the genomic regulatory regions of eight upregulated DEGs, including Tnf and Ptgs2. In aging cochleae, major proinflammatory molecules, IL1B and IL18rap, were upregulated by 6 months of age and thereafter. Remarkable upregulations of seven immune-related genes (Casp1, IL18r1, IL1B, Card9, Clec4e, Ifit1, and Tlr9) occurred at an advanced stage (between 9 and 12 months of age) of ARHL. Immunohistochemistry analysis of cochlear sections from the 12-month-old mice indicated that IL-18r1 and IL-1B were localized to the spiral ligament, spiral limbus, and organ of Corti. The two NF-κB-interacting inflammatory molecules, TNFα and PTGS2, immunolocalized ubiquitously in cochlear structures, including the lateral wall (the stria vascularis and spiral ligament), in the histological sections of aged cochleae. IBA1-positive macrophages were observed in the stria vascularis and spiral ligament in aged mice. Therefore, inflammatory and immune reactions are modulated in aged cochlear tissues with ARHL.Kensuke UraguchiYukihide MaedaJunko TakaharaRyotaro OmichiShohei FujimotoShin KariyaKazunori NishizakiMizuo AndoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258977 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kensuke Uraguchi
Yukihide Maeda
Junko Takahara
Ryotaro Omichi
Shohei Fujimoto
Shin Kariya
Kazunori Nishizaki
Mizuo Ando
Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss.
description Epidemiological data suggest that inflammation and innate immunity play significant roles in the pathogenesis of age-related hearing loss (ARHL) in humans. In this mouse study, real-time RT-PCR array targeting 84 immune-related genes revealed that the expressions of 40 genes (47.6%) were differentially regulated with greater than a twofold change in 12-month-old cochleae with ARHL relative to young control mice, 33 (39.3%) of which were upregulated. These differentially regulated genes (DEGs) were involved in functional pathways for cytokine-cytokine receptor interaction, chemokine signaling, TNF signaling, and Toll-like receptor signaling. An NF-κB subunit, Nfkb1, was upregulated in aged cochleae, and bioinformatic analyses predicted that NF-κB would interact with the genomic regulatory regions of eight upregulated DEGs, including Tnf and Ptgs2. In aging cochleae, major proinflammatory molecules, IL1B and IL18rap, were upregulated by 6 months of age and thereafter. Remarkable upregulations of seven immune-related genes (Casp1, IL18r1, IL1B, Card9, Clec4e, Ifit1, and Tlr9) occurred at an advanced stage (between 9 and 12 months of age) of ARHL. Immunohistochemistry analysis of cochlear sections from the 12-month-old mice indicated that IL-18r1 and IL-1B were localized to the spiral ligament, spiral limbus, and organ of Corti. The two NF-κB-interacting inflammatory molecules, TNFα and PTGS2, immunolocalized ubiquitously in cochlear structures, including the lateral wall (the stria vascularis and spiral ligament), in the histological sections of aged cochleae. IBA1-positive macrophages were observed in the stria vascularis and spiral ligament in aged mice. Therefore, inflammatory and immune reactions are modulated in aged cochlear tissues with ARHL.
format article
author Kensuke Uraguchi
Yukihide Maeda
Junko Takahara
Ryotaro Omichi
Shohei Fujimoto
Shin Kariya
Kazunori Nishizaki
Mizuo Ando
author_facet Kensuke Uraguchi
Yukihide Maeda
Junko Takahara
Ryotaro Omichi
Shohei Fujimoto
Shin Kariya
Kazunori Nishizaki
Mizuo Ando
author_sort Kensuke Uraguchi
title Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss.
title_short Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss.
title_full Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss.
title_fullStr Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss.
title_full_unstemmed Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss.
title_sort upregulation of a nuclear factor-kappa b-interacting immune gene network in mice cochleae with age-related hearing loss.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/22742bdcaa764614b741cc24671168b6
work_keys_str_mv AT kensukeuraguchi upregulationofanuclearfactorkappabinteractingimmunegenenetworkinmicecochleaewithagerelatedhearingloss
AT yukihidemaeda upregulationofanuclearfactorkappabinteractingimmunegenenetworkinmicecochleaewithagerelatedhearingloss
AT junkotakahara upregulationofanuclearfactorkappabinteractingimmunegenenetworkinmicecochleaewithagerelatedhearingloss
AT ryotaroomichi upregulationofanuclearfactorkappabinteractingimmunegenenetworkinmicecochleaewithagerelatedhearingloss
AT shoheifujimoto upregulationofanuclearfactorkappabinteractingimmunegenenetworkinmicecochleaewithagerelatedhearingloss
AT shinkariya upregulationofanuclearfactorkappabinteractingimmunegenenetworkinmicecochleaewithagerelatedhearingloss
AT kazunorinishizaki upregulationofanuclearfactorkappabinteractingimmunegenenetworkinmicecochleaewithagerelatedhearingloss
AT mizuoando upregulationofanuclearfactorkappabinteractingimmunegenenetworkinmicecochleaewithagerelatedhearingloss
_version_ 1718374752086654976