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...
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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) |
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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 |
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