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

Hiroshi Yamamoto, Irina Omelchenko, Xiao Shi, Alfred Nuttall

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 - 2009

Fingerprint

NF-kappa B
Inner Ear
Acoustics
Signal Transduction
Cochlea
Vascular Cell Adhesion Molecule-1
Stria Vascularis
Nitric Oxide Synthase Type II
Reperfusion Injury
Reverse Transcriptase Polymerase Chain Reaction
Vascular Diseases
Confocal Microscopy
Transcription Factors
Up-Regulation
Ischemia
Hemodynamics
Immunohistochemistry

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

The influence of NF-κB signal-transduction pathways on the murine inner ear by acoustic overstimulation. / Yamamoto, Hiroshi; Omelchenko, Irina; Shi, Xiao; Nuttall, Alfred.

In: Journal of Neuroscience Research, Vol. 87, No. 8, 2009, p. 1832-1840.

Research output: Contribution to journalArticle

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AB - 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.

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