羊胎素对暴露于白细胞介素-1β的髓核细胞的保护作用椎间盘退化细胞模型中 TLR4/MyD88 通路的参与

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2024-09-23 DOI:10.1016/j.taap.2024.117110

Junfeng Xia , Di Jia , Jianlong Wu

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引用次数: 0

摘要

椎间盘退变（IDD）会引起腰背痛、椎间盘突出和椎管狭窄等多种症状，从而导致高昂的社会和经济成本。阿尔皮内脂具有抗炎潜力，但其对 IDD 的影响尚不明确。在此，我们研究了羊齿宁对 IDD 的影响。为了模拟 IDD 的体外模型，髓核细胞（NPCs）暴露于白细胞介素 1β (IL-1β)。用 CCK-8 检测法评估 NPC 的活力。通过 qRT-PCR 和 Western 印迹检测了 Toll 样受体 4（TLR4）、髓样分化初级反应蛋白 88（MyD88）、凝集素、胶原蛋白-2 和基质金属蛋白酶-3（MMP-3）的表达。免疫印迹法检测了 B 细胞淋巴瘤-2（Bcl-2）、Bcl-2 相关蛋白 X（Bax）和裂解的 Caspase-3 的蛋白水平。流式细胞术检测评估了鼻咽癌细胞的凋亡情况。用酶联免疫吸附试剂盒检测炎症因子的含量。结果表明，羊胎素抑制了 IL-1β 诱导的 TLR4/MyD88 通路激活和鼻咽癌细胞的凋亡。羊胎素可减轻 IL-1β 引起的鼻咽癌炎症反应和氧化应激。此外，alpinetin 还能通过提高凝集素和胶原蛋白-2 的表达以及降低 MMP-3 的表达，减轻 IL-1β 对 NPC 细胞外基质（ECM）变性的影响。TLR4的上调中和了金线莲素对IL-1β暴露的NPC的影响。总之，alpinetin 通过使 TLR4/MyD88 通路失活，抑制了 IL-1β 诱导的 NPC 细胞凋亡、炎症反应、氧化应激和 ECM 降解。

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Protective effects of alpinetin against interleukin-1β-exposed nucleus pulposus cells: Involvement of the TLR4/MyD88 pathway in a cellular model of intervertebral disc degeneration

Intervertebral disc degeneration (IDD) causes a variety of symptoms such as low back pain, disc herniation, and spinal stenosis, which can lead to high social and economic costs. Alpinetin has an anti-inflammatory potential, but its effect on IDD is unclear. Herein, we investigated the effect of alpinetin on IDD. To mimic an in vitro model of IDD, nucleus pulposus cells (NPCs) were exposed to interleukin 1β (IL-1β). The viability of NPCs was assessed by CCK-8 assay. The expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), aggrecan, collagen-2, and matrix metalloproteinase-3 (MMP-3) was examined by qRT-PCR and western blotting. The protein levels of B cell lymphoma-2 (Bcl-2), Bcl-2-associated protein X (Bax), and cleaved caspase-3 were scrutinized by western blotting. The flow cytometry assay was performed to assess apoptosis of NPCs. The contents of inflammatory factors were examined by ELISA kits. Results showed that alpinetin repressed IL-1β-tempted activation of the TLR4/MyD88 pathway and apoptosis in NPCs. Alpinetin alleviated IL-1β-tempted inflammatory responses and oxidative stress in NPCs. Moreover, alpinetin lessened IL-1β-tempted extracellular matrix (ECM) degeneration in NPCs by enhancing the expression of aggrecan and collagen-2 and reducing the expression of MMP-3. The effects of alpinetin on IL-1β-exposed NPCs were neutralized by TLR4 upregulation. In conclusion, alpinetin repressed IL-1β-tempted apoptosis, inflammatory responses, oxidative stress, and ECM degradation in NPCs through the inactivation of the TLR4/MyD88 pathway.

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.