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...
Guardado en:
| Autores principales: | , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/22742bdcaa764614b741cc24671168b6 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| Sumario: | 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. |
|---|