肉毒杆菌毒素 A 可抑制 BV-2 小胶质细胞的炎症反应。

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon Pub Date : 2024-11-22 DOI:10.1016/j.toxicon.2024.108182

Mario Brito da Silva Filho , Gabriela Aniceto , Patrícia Maria Fernandes , Iara Gonçalves Aquino , Gustavo Duarte Mendes , Marcelo Henrique Napimoga , Juliana Trindade Clemente-Napimoga , Henrique Ballassini Abdalla

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引用次数: 0

摘要

我们之前的研究证明了 A 型肉毒毒素（BoNT/A）在颞下颌关节类风湿性关节炎临床前模型中的镇痛效果，并提出 BoNT/A 到达尾状核下后会降低神经源环境。然而，BoNT/A 是否直接调节小胶质细胞的活性尚不得而知。因此，本研究调查了 BoNT/A 在不同炎症条件下对小鼠小胶质细胞系（BV-2）的影响。不同浓度的 BoNT/A（从 0.3125 U/mL到 20 U/mL）可使细胞存活和增殖 24 小时。用卡拉胶（300μg/mL）或脂多糖（LPS）（20ng/mL）诱导细胞。用 PCR-RT 对 IL-1β、IL-6、IL-18、TNF-α、Ikkβ、p65、Iba1 的基因表达进行定量。上清液用于测定 IL-1β、IL-6 和 TNF-α 的水平。所有数据的显著性水平均定为 5%。总体而言，数据分析显示，BoNT/A 1.25 U/mL对细胞活力和增殖的影响最大。此外，在两种刺激（角叉菜胶和 LPS）下，与炎症反应相关的基因在 BoNT/A 的存在下均出现下调。最后，BoNT/A 对 IL-1β 和 TNF-α 蛋白水平的降低具有时间和剂量依赖性。总之，我们的研究结果表明，BoNT/A 可直接调节炎症背景下小胶质细胞的活动，考虑到其潜在的免疫调节作用，这为使用 BoNT/A 开辟了新的前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Botulinum toxin A dampened inflammatory response in BV-2 microglial cells

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Botulinum toxin A dampened inflammatory response in BV-2 microglial cells

Our previous studies have demonstrated the analgesic effects of botulinum toxin type A (BoNT/A) in a pre-clinical model of rheumatoid arthritis of the temporomandibular joint, where we proposed that BoNT/A decreases the neurogenic milieu after reaching the subnucleus caudalis. However, it is unknown whether BoNT/A directly regulates microglial cell activity. Therefore, the present study investigates the effects of BoNT/A on a microglial murine cell lineage (BV-2) in different inflammatory conditions. Cellular viability and proliferation were carried out with different concentrations of BoNT/A (ranging from 0.3125 to 20 U/mL) for 24 h. Cells were primed with carrageenan (300 μg/mL) or Lipopolysaccharides (LPS) (20 ng/mL). The gene expression of IL-1β, IL-6, IL-18, TNF-α, Ikkβ, p65, Iba1 were quantified using PCR-RT. The supernatant was used to determine IL-1β, IL-6, and TNF-α levels. For all data, the significance level was set at 5%. Overall, data analysis revealed that BoNT/A 1.25 U/mL exhibited the greatest effect cell viability and proliferation. In addition, genes associated with inflammatory response in both stimuli (carrageenan and LPS) were downregulated in the presence of BoNT/A. Lastly, BoNT/A mitigates the protein levels of IL-1β and TNF-α in a time and dose-dependent manner. In conclusion, our results revealed that BoNT/A directly modulates the microglial cells' activities in an inflammatory context, opening new perspectives for using BoNT/A, considering its potential immunomodulatory effect.

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来源期刊

Toxicon 医学-毒理学

CiteScore

4.80

自引率

10.70%

发文量

358

审稿时长

68 days

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