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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\u2013cytokine receptor interaction, chemokine signaling, TNF signaling, and Toll-like receptor signaling. An NF-\u03baB subunit, <jats:italic>Nfkb1<\/jats:italic>, was upregulated in aged cochleae, and bioinformatic analyses predicted that NF-\u03baB would interact with the genomic regulatory regions of eight upregulated DEGs, including <jats:italic>Tnf<\/jats:italic> and <jats:italic>Ptgs2<\/jats:italic>. In aging cochleae, major proinflammatory molecules, <jats:italic>IL1B<\/jats:italic> and <jats:italic>IL18rap<\/jats:italic>, were upregulated by 6 months of age and thereafter. Remarkable upregulations of seven immune-related genes (<jats:italic>Casp1<\/jats:italic>, <jats:italic>IL18r1<\/jats:italic>, <jats:italic>IL1B<\/jats:italic>, <jats:italic>Card9<\/jats:italic>, <jats:italic>Clec4e<\/jats:italic>, <jats:italic>Ifit1<\/jats:italic>, and <jats:italic>Tlr9<\/jats:italic>) 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-\u03baB-interacting inflammatory molecules, TNF\u03b1 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.<\/jats:p>","DOI":"10.1371\/journal.pone.0258977","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T17:27:35Z","timestamp":1634923655000},"page":"e0258977","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Upregulation of a nuclear factor-kappa B-interacting immune gene network in mice cochleae with age-related hearing loss"],"prefix":"10.1371","volume":"16","author":[{"given":"Kensuke","family":"Uraguchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8106-9055","authenticated-orcid":true,"given":"Yukihide","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Takahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryotaro","family":"Omichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Kariya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Nishizaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuo","family":"Ando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"pone.0258977.ref001","unstructured":"National Institute on Deafness and Other Communication Disorders, Accessed in December, 2019. 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