摘要
背景:在关节创伤后,创伤后炎症级联驱动关节退化。我们的目的是评估过表达免疫调节细胞因子IL-10的AAV5对软骨细胞的转导是否会对用IL-1β刺激的沉淀培养物产生保护作用。 方法:从3只健康马中分离软骨细胞,并以1×105vg /细胞的剂量用AAV5-IL-10转导。通过离心形成软骨细胞沉淀,并在转导后48小时开始用IL-1β刺激。在培养2,6和14天后,收集上清液用于细胞因子分析,并从细胞中分离RNA用于基因表达分析。还收集沉淀用于生化分析。 结果:软骨细胞的转导导致IL-10表达显着增加。 IL-1β刺激进一步增强IL-10表达。 IL-10过表达导致IL-1β和ADAMTS4的表达显着降低。 PGE2合成也显着降低。 IL-1不能挽救IL-1β介导的GAG合成抑制。 结论:IL-10的过度表达调节软骨细胞的炎症反应,这可以减轻创伤后关节中促炎级联反应的一些有害作用。 AAV5-IL-10导致IL-10在软骨细胞中的有效和持续过表达,并且可以代表预防骨关节炎的可行治疗选择
关键词: 骨关节炎,基因治疗,AAV,IL-10,免疫调节,软骨细胞颗粒,细胞因子。
Current Gene Therapy
Title:AAV-mediated Overexpression of IL-10 Mitigates the Inflammatory Cascade in Stimulated Equine Chondrocyte Pellets
Volume: 18 Issue: 3
关键词: 骨关节炎,基因治疗,AAV,IL-10,免疫调节,软骨细胞颗粒,细胞因子。
摘要: Background: Following joint trauma, a posttraumatic inflammatory cascade drives degeneration of the joint. We aimed to assess whether transduction of chondrocytes with AAV5 overexpressing the immunomodulatory cytokine IL-10 would have protective effects in pellet cultures stimulated with IL-1β.
Methods: Chondrocytes were isolated from 3 healthy horses and were transduced with AAV5-IL-10 at a dose of 1 x 105vg/cell. Chondrocyte pellets were formed by centrifugation and were stimulated with IL-1β starting 48 hours following transduction. After 2, 6 and 14 days in culture, supernatants were collected for cytokine analysis and RNA was isolated from cells for gene expression analysis. Pellets were also collected for biochemical analysis.
Results: Transduction of chondrocytes led to significant increases in IL-10 expression. IL-10 expression was further enhanced by IL-1β stimulation. IL-10 overexpression led to significantly decreased expression of IL-1β and ADAMTS4. PGE2 synthesis was also significantly decreased. IL-1β mediated suppression of GAG synthesis was not rescued by IL-10.
Conclusions: Overexpression of IL-10 modulates the inflammatory response in chondrocytes, which may mitigate some of the deleterious effects of pro-inflammatory cascades in the posttraumatic joint. AAV5-IL-10 led to efficient and sustained overexpression of IL-10 in chondrocytes and could represent a viable treatment option for preventing osteoarthritis.
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AAV-mediated Overexpression of IL-10 Mitigates the Inflammatory Cascade in Stimulated Equine Chondrocyte Pellets, Current Gene Therapy 2018; 18 (3) . https://dx.doi.org/10.2174/1566523218666180510165123
DOI https://dx.doi.org/10.2174/1566523218666180510165123 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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