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

by Kensuke Uraguchi, Yukihide Maeda, Junko Takahara, Ryotaro Omichi, Shohei Fujimoto, Shin Kariya, Kazunori Nishizaki, Mizuo Ando 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 different ially 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 signali ng, 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, includingTnf andPtgs2. In aging cochleae, major proinflammatory molecules,IL1B andIL18rap, were upregulated by 6 months of age and thereafter. Remarkable upregulations of seven immune-related genes (Casp1,IL18r1,IL1B,Card9,Clec4e,Ifit1, andTlr9) 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-interactin...
Source: PLoS One - Category: Biomedical Science Authors: Source Type: research