Zhang Na, Song Yongdong, Wang Hanyue, Li Xiaofei, Lyu Yafeng, Liu Jiahui, Mu Yurong, Wang Yan, Lu Yao, Li Guorong, Fan Zhaomin, Wang Haibo, Zhang Daogong, Li Na
Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, Shandong, China.
Shandong Provincial Vertigo Dizziness Medical Center, Jinan, Shandong, China.
Cell Death Discov. 2024 Nov 20;10(1):476. doi: 10.1038/s41420-024-02246-2.
Ménière's disease (MD) is a complex inner ear disorder characterized by a range of symptoms, with its pathogenesis linked to immune-related mechanisms. Our previous research demonstrated that IL-1β maturation and release can trigger cell pyroptosis, exacerbating the severity of the endolymphatic hydrops in a mouse model; however, the specific mechanism through which IL-1β influences MD symptoms remains unclear. This study conducted on patients with MD examined changes in protein signatures in the vestibular end organs (VO) and endolymphatic sac (ES) using mass spectrometry. Gene ontology and protein pathway analyses showed that differentially expressed proteins in the ES are closely related to adhesion, whereas those in the VO are related to synapse processes. Additionally, the study found elevated expression of Glutaminase (GLS) in the VO of MD patients compared to controls. Further investigations revealed that IL-1β increased glutamate levels by upregulating GLS expression in HEI-OC1 cells. Treatment with a GLS inhibitor or an IL-1β receptor antagonist alleviated auditory-vestibular dysfunction and reduced glutamate levels in mice with endolymphatic hydrops. These findings collectively suggest that imbalanced neurotransmitter release and immune responses contribute to the pathology of MD, potentially explaining the hearing loss and vertigo associated with the disease and offering new avenues for therapeutic interventions.
梅尼埃病（MD）是一种复杂的内耳疾病，其特征为一系列症状，其发病机制与免疫相关机制有关。我们之前的研究表明，白细胞介素-1β（IL-1β）的成熟和释放可触发细胞焦亡，在小鼠模型中加剧内淋巴积水的严重程度；然而，IL-1β影响MD症状的具体机制仍不清楚。本研究对MD患者进行了研究，使用质谱法检测了前庭终器（VO）和内淋巴囊（ES）中蛋白质特征的变化。基因本体和蛋白质通路分析表明，ES中差异表达的蛋白质与黏附密切相关，而VO中的蛋白质与突触过程有关。此外，研究发现MD患者VO中谷氨酰胺酶（GLS）的表达高于对照组。进一步研究表明，IL-1β通过上调HEI-OC1细胞中GLS的表达来增加谷氨酸水平。用GLS抑制剂或IL-1β受体拮抗剂治疗可减轻内淋巴积水小鼠的听觉-前庭功能障碍并降低谷氨酸水平。这些研究结果共同表明，神经递质释放和免疫反应失衡导致了MD的病理过程，这可能解释了与该疾病相关的听力损失和眩晕，并为治疗干预提供了新的途径。
