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• W2098864202 endingPage "3372" @default.
• W2098864202 startingPage "3361" @default.
• W2098864202 abstract "ABSTRACT Inner ear dysfunction secondary to chronic otitis media (OM), including high-frequency sensorineural hearing loss or vertigo, is not uncommon. Although chronic middle ear inflammation is believed to cause inner ear dysfunction by entry of OM pathogen components or cytokines from the middle ear into the inner ear, the underlying mechanisms are not well understood. Previously, we demonstrated that the spiral ligament fibrocyte (SLF) cell line up-regulates monocyte chemotactic protein 1 (MCP-1) expression after treatment with nontypeable Haemophilus influenzae (NTHI), one of the most common OM pathogens. We hypothesized that the SLF-derived MCP-1 plays a role in inner ear inflammation secondary to OM that is responsible for hearing loss and dizziness. The purpose of this study was to investigate the signaling pathway involved in NTHI-induced MCP-1 up-regulation in SLFs. Here we show for the first time that NTHI induces MCP-1 up-regulation in the SLFs via Toll-like receptor 2 (TLR2)-dependent activation of NF-κB. TLR2 −/− - and MyD88 −/− -derived SLFs revealed involvement of TLR2 and MyD88 in NTHI-induced MCP-1 up-regulation. Studies using chemical inhibitors and dominant-negative constructs demonstrated that it is mediated by the IκKβ-dependent IκBα phosphorylation and NTHI-induced NF-κB nuclear translocation. Furthermore, we demonstrated that the binding of NF-κB to the enhancer region of MCP-1 is involved in this up-regulation. In addition, we have identified a potential NF-κB motif that is responsive and specific to certain NTHI molecules or ligands. Further studies are necessary to reveal specific ligands of NTHI that activate host receptors. These results may provide us with new therapeutic strategies for prevention of inner ear dysfunction secondary to chronic middle ear inflammation." @default.
• W2098864202 created "2016-06-24" @default.
• W2098864202 creator A5001942999 @default.
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• W2098864202 creator A5075262916 @default.
• W2098864202 date "2007-07-01" @default.
• W2098864202 modified "2023-10-16" @default.
• W2098864202 title "Toll-Like Receptor 2-Dependent NF-κB Activation Is Involved in Nontypeable <i>Haemophilus influenzae</i> -Induced Monocyte Chemotactic Protein 1 Up-Regulation in the Spiral Ligament Fibrocytes of the Inner Ear" @default.
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