Arroul-Lammali Amina, Rahal Fadia, Chetouane Radia, Djeraba Zineb, Medjeber Oussama, Ladjouze-Rezig Aicha, Touil-Boukoffa Chafia
a Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Team, Faculty of Biological Sciences , USTHB (University of Sciences and Technology) , Algiers , Algeria.
b Rheumatology Department , Ben aknoun hospital EHS , Algiers , Algeria.
Immunopharmacol Immunotoxicol. 2017 Apr;39(2):87-96. doi: 10.1080/08923973.2017.1285919. Epub 2017 Feb 10.
Rheumatoid arthritis (RA) is a chronic autoimmune disease. The pathophysiology of RA implicates several mediators such as nitric oxide (NO) and cytokines such as interleukin-6 (IL-6), which is deeply involved in the main characteristics of RA. Furthermore, all-trans retinoic acid (ATRA) is an active vitamin A derivative well-known to have diverse immunomodulatory actions. In our study, we investigated first, the ex vivo immunomodulatory potential of ATRA on NO pathway by peripheral blood mononuclear cells (PBMCs) from Algerian RA patients. Then, we assessed the possible regulatory effect of ATRA on NO production induced by IL-6. PBMCs isolated from active and inactive RA patients and healthy controls were cultured with different concentrations of IL-6 or/with ATRA. NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence test. Our results revealed a high NO production during active RA. We noticed that while IL-6 induced a high NO production and iNOS expression, ATRA downregulated both. ATRA also inhibited nuclear NF-κB translocation. Interestingly, it seems that NO production mediated by IL-6 on PBMCs of RA patients is downregulated by ATRA. Taken together, our results highlight the immunomodulatory effect of ATRA on NO pathway in RA patients and its possible role in regulating IL-6-mediated NO production. All these findings suggest its potential therapeutic role during RA.
类风湿关节炎（RA）是一种慢性自身免疫性疾病。RA的病理生理学涉及多种介质，如一氧化氮（NO）和细胞因子，如白细胞介素-6（IL-6），其深度参与RA的主要特征。此外，全反式维甲酸（ATRA）是一种活性维生素A衍生物，众所周知具有多种免疫调节作用。在我们的研究中，我们首先研究了ATRA对来自阿尔及利亚RA患者外周血单核细胞（PBMC）的NO途径的体外免疫调节潜力。然后，我们评估了ATRA对IL-6诱导的NO产生的可能调节作用。将从活动期和非活动期RA患者及健康对照中分离的PBMC与不同浓度的IL-6或/和ATRA一起培养。使用Griess方法评估NO的产生。通过免疫荧光试验分析诱导型一氧化氮合酶的表达和NF-κB的活性。我们的结果显示活动期RA期间NO产生较高。我们注意到，虽然IL-6诱导了较高的NO产生和诱导型一氧化氮合酶表达，但ATRA下调了两者。ATRA还抑制了核NF-κB易位。有趣的是，似乎ATRA下调了IL-6对RA患者PBMC介导的NO产生。综上所述，我们的结果突出了ATRA对RA患者NO途径的免疫调节作用及其在调节IL-6介导的NO产生中的可能作用。所有这些发现表明其在RA期间的潜在治疗作用。
