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通过用负载二甲基砜的 PLGA 纳米粒处理成纤维样滑膜细胞(FLS)减轻氧化应激来改善类风湿关节炎的炎症。

Amelioration of inflammation through reduction of oxidative stress in rheumatoid arthritis by treating fibroblast-like synoviocytes (FLS) with DMF-loaded PLGA nanoparticles.

机构信息

Department of Immunology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.

Department of Immunology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran; Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

出版信息

Int Immunopharmacol. 2024 Mar 10;129:111617. doi: 10.1016/j.intimp.2024.111617. Epub 2024 Feb 3.

Abstract

BACKGROUND

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory condition, and Dimethyl fumarate (DMF) is known for inducing antioxidant enzymes and reducing reactive oxygen species (ROS). Fibroblast-like synoviocytes (FLS) contribute to joint damage by releasing interleukins (IL-1β, IL-6, and IL-8) in response to ROS. Given ROS's impact on FLS acquiring an invasive phenotype, our study explored the effects of poly lactic-co-glycolic acid (PLGA) nanoparticles containing DMF on the expression of the HO-1 enzyme and the inflammatory cytokines IL-1β, IL-6, and IL-8 in FLS cells.

METHODS

In this study, we evaluated and compared the impact of Free-DMF and PLGA-DMF, on the gene expression of the HO-1 and inflammatory cytokines (IL-1β, IL-6, and IL-8) in FLS cells derived from 13 patients with rheumatoid arthritis. qRT-PCR method was used to quantify the gene expression levels.

RESULTS

PLGA-DMF nanoparticles demonstrated a significant increase in HO-1 expression and a significant decrease in IL-1β gene expression. Also, a significant decrease in IL-6 gene expression was seen under the effect of Free-DMF. These results indicate the potential effectiveness of PLGA-DMF nanoparticles in reducing inflammation and improving rheumatoid arthritis symptoms.

DISCUSSION

According to the findings, PLGA-DMF nanoparticles are expected to be effective in reducing inflammation and improving the symptoms of rheumatoid arthritis. Also, further studies on other factors affected by oxidative stress such as cell invasion factors and survival factors after the effect of PLGA-DMF nanoparticle are recommended.

摘要

背景

类风湿关节炎(RA)是一种慢性自身免疫性炎症性疾病,二甲基富马酸(DMF)以诱导抗氧化酶和减少活性氧(ROS)而闻名。成纤维样滑膜细胞(FLS)通过释放白细胞介素(IL-1β、IL-6 和 IL-8)对 ROS 做出反应,从而导致关节损伤。鉴于 ROS 对 FLS 获得侵袭表型的影响,我们的研究探讨了含有 DMF 的聚乳酸-共-羟基乙酸(PLGA)纳米颗粒对 FLS 细胞中 HO-1 酶和炎症细胞因子 IL-1β、IL-6 和 IL-8 表达的影响。

方法

在这项研究中,我们评估并比较了游离 DMF 和 PLGA-DMF 对 13 例类风湿关节炎患者来源的 FLS 细胞中 HO-1 和炎症细胞因子(IL-1β、IL-6 和 IL-8)基因表达的影响。qRT-PCR 法用于定量基因表达水平。

结果

PLGA-DMF 纳米颗粒显著增加了 HO-1 的表达,并显著降低了 IL-1β 的基因表达。此外,游离 DMF 的作用下还观察到 IL-6 基因表达的显著下降。这些结果表明 PLGA-DMF 纳米颗粒在减轻炎症和改善类风湿关节炎症状方面具有潜在的有效性。

讨论

根据研究结果,PLGA-DMF 纳米颗粒有望有效减轻炎症并改善类风湿关节炎症状。此外,建议在 PLGA-DMF 纳米颗粒作用后进一步研究其他受氧化应激影响的因素,如细胞侵袭因子和生存因子。

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