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

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

Research output: Contribution to journalArticle

31 Scopus citations

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-jB 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.

Original languageEnglish (US)
Pages (from-to)1832-1840
Number of pages9
JournalJournal of Neuroscience Research
Volume87
Issue number8
DOIs
StatePublished - Jun 2 2009

Keywords

  • ICAM-1
  • INOS
  • Noise exposure
  • Stria vascularis
  • VCAM-1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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