Yamamoto Hiroshi, Omelchenko Irina, Shi Xiaorui, Nuttall Alfred L
Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon 97239-3098, USA.
J Neurosci Res. 2009 Jun;87(8):1832-40. doi: 10.1002/jnr.22018.
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.
核因子-κB（NF-κB）是一类可诱导的转录因子家族，是宿主免疫和炎症反应的重要调节因子。NF-κB信号通过经典和/或非经典途径在多种刺激下被激活。NF-κB信号转导途径的过度作用经常导致自身损伤现象，如过敏性疾病、血管疾病和缺血再灌注神经元损伤。在内耳中，NF-κB的作用尚未明确，因为激活的NF-κB信号在耳毒性刺激后可能诱导细胞保护和细胞毒性靶基因。在本研究中，我们研究了经典和非经典途径中NF-κB对声学过度刺激（117 dB/SPL/2小时）的反应，并跟踪了耳蜗外侧壁（CLW）和耳蜗其余部分（RoC）中炎症因子（诱导型一氧化氮合酶[iNOS]、细胞间黏附分子-1[ICAM-1]和血管细胞黏附分子-1[VCAM-1]）的变化。通过免疫组织化学结合共聚焦显微镜和逆转录聚合酶链反应技术，我们在转录水平上发现了NF-κB家族成员（NF-κB1、2、RelA和RelB）的反应。NF-κB信号传导后，CLW和RoC中的炎症因子显著增加。此外，在蛋白质水平上，在血管纹毛细血管周围的组织中观察到黏附分子（ICAM-1和VCAM-1）的显著表达。这些结果表明，声学过度刺激导致NF-κB信号传导在内耳中过度表达炎症因子，黏附分子（ICAM-1和VCAM-1）和iNOS的上调可能影响血管纹中的血流动力学和细胞完整性。
