title: The influence of NF-kappaB signal-transduction pathways on the murine inner ear by acoustic overstimulation.
abstract: Nuclear factor-kappa B (NF-kappaB) comprises a family of inducible transcription factors that serve as important regulators of the host immune and inflammatory responses. The NF-kappaB signals are activated via the canonical and/or noncanonical pathways in response to diverse stimuli. The excessive action of NF-kappaB signal-transduction pathways frequently causes self-injurious phenomena such as allergic diseases, vascular disorders, and ischemia-reperfusion neuronal damage. In the inner ear, the role of NF-kappaB has not been clarified because the activated NF-kappaB signals potentially induce both cytoprotective and cytotoxic target genes after ototoxic stimulation. In the present study, we investigated the response of NF-kappaB in both the canonical and noncanonical pathways to acoustic overstimulation (117 dB/SPL/2 hr) and followed the change of inflammatory factors (inducible nitric oxide synthase [iNOS], intracellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1]) in the cochlear lateral wall (CLW) and the rest of cochlea (RoC). By means of immunohistochemistry combined with confocal microscopy and reverse transcriptase-polymerase chain reaction techniques, we found the response of NF-kappaB family members (NF-kappa B1, 2, RelA, and RelB) at the transcription level. After the NF-kappaB signaling, the inflammatory factors were significantly increased in the CLW and the RoC. Additionally, at the protein level, the prominent expression of adhesion molecules (ICAM-1 and VCAM-1) was observed in the tissue around the capillaries in the stria vascularis. These results show that acoustic overstimulation causes the NF-kappaB signaling to overexpress the inflammatory factors in the inner ear, and the up-regulation of the adhesion molecules (ICAM-1 and VCAM-1) and iNOS potentially influence the hemodynamics and the cellular integrity in the stria vascularis.
authors.affiliation: Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon 97239-3098, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Irina
authors.initials: I
authors.lastname: Omelchenko
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Shi
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Nuttall
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D003051:Cochlea / Q000378:metabolism* / Q000503:physiopathology; D006198:Hair Cells, Auditory / Q000378:metabolism; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008144:Loudness Perception / Q000502:physiology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism*; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013316:Stria Vascularis / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C090509:Icam1 protein, mouse; D018836:Inflammation Mediators; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse