The relationship between cochlear blood flow disorder and NF‐kB activation by loud sound situation

Abstract

Nuclear factor‐kappa B (NF‐κB) plays an essential role in the regulation of genes involved in various biological processes, such as inflammation, immune responses, neuronal development, and cellular apoptosis. NF‐κB activation can be achieved through two main pathways. The canonical (classical) pathway is known to be involved in the response of various cell types to pathogen associated molecules as well as proinflammatory cytokines, such as tumor necrosis factor alpha (TNF‐α) and interleukin‐1 (IL‐1). The noncanonical (alternative) is activated by a different specific set of stimuli, including B‐cell activating factor (BAFF), lymphotoxinβ, and CD40L.In this study, using immunohistochemistry and immunoblot analysis, we determined whether one or both NF‐κB pathways, canonical (classical) or noncanonical (alternative), involved in loud‐sound induced cellular damages mechanism in guinea pig cochlea. In control (non‐sound stimulated) condition, we found that there was no detectable phosphoralated P65 in canonical pathway or P100 in the noncanonical pathway in both organ of Corti and cochlear lateral wall. However, NF‐κB activation related P65 phosphorylation was detected in the inner ear immediately following loud‐sound exposure at 120dB SPL/3hr for a day. There was no phosphorylation of p100 at any time periods following loud sound stimulation. These results suggest that loud‐sound stress activates NF‐κB dependent on P65 (canonical) pathway but not P100 (non‐canonical) pathway in the response to loud‐sound induced cellular damage. Supported by NIH/NIDCD R01 DC 00105, 008888 and 005983.