当前位置: X-MOL 学术Inflammopharmacology › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Beneficial effect of dimethyl fumarate on experimental autoimmune uveitis is dependent of pro-inflammatory markers immunomodulation
Inflammopharmacology ( IF 4.6 ) Pub Date : 2021-09-13 , DOI: 10.1007/s10787-021-00864-1
Moussa Labsi 1 , Imene Soufli 1 , Houda Belguendouz 1 , Sara Djebbara 1 , Leila Hannachi 2 , Zine-Charaf Amir 2 , Chafia Touil-Boukoffa 1
Affiliation  

Autoimmune uveitis is an inflammatory disease of the eye and is one of the major causes of blindness worldwide. Experimental autoimmune uveoretinitis (EAU) constitutes an animal disease model of human endogenous uveitis. In our study, we investigated the immunomodulatory effect of dimethyl fumarate (DMF) using bovine retinal extract-induced uveitis in a Female Wistar rats. To evaluate the in vivo efficacy, Female Wistar rats were divided into seven experimental groups: control group (n = 5), consisting of non-immunized animals; Uveoretinitis (n = 5), and DMF/Uveoretinitis groups (n = 15), which received a subcutaneous injection of bovine retinal extract emulsified in complete Freund’s adjuvant; MC group (n = 5), treated by daily intragastric administration of methylcellulose 0.08% in tap water; DMF group, consisting of control positive group, rats received daily oral gavage administration of 500 μL of dimethyl fumarate at 100 mg/Kg dissolved in 0.08% methylcellulose in tap water (n = 5). On day 14 post immunization, the rats were then euthanized and associated indications were investigated to evaluate the therapeutic efficacy. Nitric oxide (NO) and TNF-α were assessed in plasma. Meanwhile, eyes were collected for histological and immunohistochemical studies. The retinal expression of iNOS, CD68, CD20, CD25, CD4, and CD8 was examined. Interestingly, DMF enhanced a significant reduction of NO and TNF-α production in the treated group. This effect was strongly related to the histological structure of eyes improvement. In the same context, a significant decrease of iNOS, CD68, and CD20 expression and CD25 increase expression were reported in retinal tissue of DMF/Uveoretinitis group in comparison to the immunized group. Collectively, our results indicate that DMF treatment has a beneficial effect in experimental autoimmune uveoretinitis and could constitute a good candidate for monitoring an ocular inflammatory diseases.



中文翻译:

富马酸二甲酯对实验性自身免疫性葡萄膜炎的有益作用依赖于促炎标志物免疫调节

自身免疫性葡萄膜炎是一种眼部炎症性疾病,是全世界失明的主要原因之一。实验性自身免疫性葡萄膜炎(EAU)构成了人类内源性葡萄膜炎的动物疾病模型。在我们的研究中,我们研究了富马酸二甲酯 (DMF) 在雌性Wistar大鼠中使用牛视网膜提取物诱导的葡萄膜炎的免疫调节作用。为了评估体内功效,将雌性Wistar大鼠分为七个实验组:对照组(n  = 5),由未免疫动物组成;葡萄膜炎(n  = 5)和DMF/葡萄膜炎组(n  = 15),接受皮下注射牛视网膜提取物在完全弗氏佐剂中乳化;MC组(n  = 5),通过每天灌胃 0.08% 的自来水中的甲基纤维素进行治疗;DMF组,由对照组阳性组组成,大鼠每天口服管饲500 μL富马酸二甲酯,浓度为100 mg/Kg,溶解在自来水中的0.08%甲基纤维素中(n = 5)。在免疫后第 14 天,对大鼠实施安乐死并研究相关适应症以评估治疗效果。在血浆中评估一氧化氮 (NO) 和 TNF-α。同时,收集眼睛进行组织学和免疫组织化学研究。检查了 iNOS、CD68、CD20、CD25、CD4 和 CD8 的视网膜表达。有趣的是,DMF 显着降低了治疗组中 NO 和 TNF-α 的产生。这种效果与眼睛改善的组织学结构密切相关。在相同情况下,与免疫组相比,DMF/葡萄膜炎组视网膜组织中 iNOS、CD68 和 CD20 表达显着降低,CD25 表达增加。集体,

更新日期:2021-09-13
down
wechat
bug