The influence of NF-kappaB signal-transduction pathways on the murine inner ear by acoustic overstimulation.

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. (c) 2009 Wiley-Liss, Inc.