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氯化钠暴露导致梅尼埃病患者白细胞介素-1β表达和加工增加。

NaCl exposure results in increased expression and processing of IL-1β in Meniere's disease patients.

机构信息

The Feinstein Institutes for Medical Research, Manhasset, NY, USA.

Department of Otolaryngology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.

出版信息

Sci Rep. 2022 Mar 23;12(1):4957. doi: 10.1038/s41598-022-08967-7.

Abstract

Meniere's disease (MD) is a chronic disease that causes episodic vertigo, fluctuating hearing loss, and aural fullness, initially managed by dietary salt reduction, and use of diuretics. Our prior research in autoimmune inner ear disease (AIED) demonstrated that in peripheral blood mononuclear cell (PBMC) from corticosteroid-resistant AIED patients, increased production, processing and release of interleukin-1β (IL-1β) is observed and hearing could be improved with use of anakinra, an interleukin-1 receptor antagonist. We have further identified that in these AIED patients, IL-1β is uniquely processed to a 28 kDa pro-inflammatory product by caspase-7. In the present study, we characterize the production, processing and release of the pro-inflammatory cytokines IL-1β and IL-6 from PBMC of MD (n = 14) patients in response to sodium chloride (NaCl), and determined the effect of the diuretic triamterene-hydrocholothiazide (T-HCTZ), or anakinra in these patients. We observed that PBMC cultured with NaCl from MD patients show processing of IL-1β to the 28 kDa product, and that this product is abrogated with T-HCTZ. Our observations are consistent with other autoimmune diseases where high concentrations of NaCl caused release of pro-inflammatory cytokines and may provide further insight as to the mechanism of disease progression in MD patients.

摘要

梅尼埃病(MD)是一种慢性疾病,会导致阵发性眩晕、波动性听力损失和耳闷,最初通过减少饮食中的盐量和使用利尿剂来治疗。我们之前在自身免疫性内耳疾病(AIED)方面的研究表明,在皮质类固醇耐药性 AIED 患者的外周血单核细胞(PBMC)中,观察到白细胞介素-1β(IL-1β)的产生、加工和释放增加,并且可以通过使用白细胞介素-1 受体拮抗剂 anakinra 来改善听力。我们进一步确定,在这些 AIED 患者中,IL-1β 被半胱天冬酶-7独特地加工为 28 kDa 的促炎产物。在本研究中,我们研究了 MD(n = 14)患者 PBMC 对氯化钠(NaCl)的反应中促炎细胞因子 IL-1β 和 IL-6 的产生、加工和释放,并确定了利尿剂阿米洛利氢氯噻嗪(T-HCTZ)或 anakinra 在这些患者中的作用。我们观察到,来自 MD 患者的 PBMC 在 NaCl 培养下会加工 IL-1β 成 28 kDa 的产物,而 T-HCTZ 则会阻止这种产物的产生。我们的观察结果与其他自身免疫性疾病一致,即在高浓度 NaCl 下会释放促炎细胞因子,这可能为 MD 患者疾病进展的机制提供了进一步的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70b7/8943007/fdd6c38629de/41598_2022_8967_Fig1_HTML.jpg

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