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

By Hiroshi Yamamoto, Irina Omelchenko, Xiaorui Shi and Alfred L. Nuttall

Abstract

Nuclear factor-kappa B (NF-ΚB) comprises a family of inducible transcription factors that serve as important regulators of the host immune and inflammatory responses. The NF-ΚB signals are activated via the canonical and/or noncanonical pathways in response to diverse stimuli. The excessive action of NF-ΚB 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-ΚB has not been clarified because the activated NF-ΚB signals potentially induce both cytoprotective and cytotoxic target genes after ototoxic stimulation. In the present study, we investigated the response of NF-ΚB 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-ΚB family members (NF-ΚB1, 2, RelA, and RelB) at the transcription level. After the NF-ΚB 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-ΚB 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. © 2009 Wiley-Liss, Inc

Publisher: Wiley Subscription Services, Inc., A Wiley Company
Year: 2009
DOI identifier: 10.1002/jnr.22018
OAI identifier: oai:deepblue.lib.umich.edu:2027.42/62147
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