Abstract：
GABBR1 receptors have been implicated in the progression of rheumatoid arthritis (RA), and p38 MAP kinase (MAPK) was shown to be downregulated by GABA and result in unchecked production of pro-inflammatory cytokine. GABBR1 is a member of GABA receptors, and it is known to be upregulated and plays a vital role in RA. Glucocorticoids are efficient therapeutics in rheumatoid arthritis (RA) and are known to regulate GABA actions; therefore, we intended to investigate the potential of glucocorticoids in RA concerning the potential pathway GABBR1/MAPK. Joint specimens were obtained from collagen-induced arthritis mouse model. A double-blind semi-quantitative analysis of vascularity, cell infiltration, as well as lining thickness by help of a 4-point scale setting was used to assess joint inflammation. Expression of GABBR1 and p38 was evaluated immunohistochemically. In vitro peripheral blood (PB), synovial fluid (SF), and mononuclear cells (MCs) were acquired from RA mice. Western blotting was used for detecting expression of GABBR1 and p38 proteins. The presence of high levels of GABBR1 and p38 was prevalent in RA joints relative to healthy joints and related to the inflammation level. Glucocorticoid treatment alters GABBR1 along with p38 protein expression in joints while reducing joint inflammation. Ex vivo and in vitro assays revealed glucocorticoids have a direct impact on p38, such as the decreased GABBR1 expression level after dexamethasone incubation with SFMC. GABBR1 together with p38 expression in RA joints depends on local inflammation and can be targeted by glucocorticoids.
摘要：
GABBR1受体与类风湿关节炎（RA）的进展有关，和p38MAP激酶（MAPK）被GABA下调，并导致促炎细胞因子的产生不受控制。GAMBR1是GABA受体的成员，众所周知，它被上调，在RA中起着至关重要的作用。糖皮质激素是类风湿关节炎（RA）的有效治疗剂，并且已知可调节GABA作用；因此，我们旨在研究糖皮质激素在RA中的潜在作用，涉及潜在途径GABBR1/MAPK。从胶原诱导的关节炎小鼠模型获得关节标本。血管的双盲半定量分析，细胞浸润,以及通过4点量表设置的衬里厚度用于评估关节炎症。免疫组织化学评估GABBR1和p38的表达。体外外周血（PB），滑液（SF），从RA小鼠获得单核细胞(MC)。Western印迹用于检测GABBR1和p38蛋白的表达。相对于健康关节，RA关节中存在高水平的GABBR1和p38，并且与炎症水平有关。糖皮质激素治疗改变关节中GABBR1和p38蛋白表达,同时减轻关节炎症。离体和体外分析显示，糖皮质激素对p38有直接影响，例如地塞米松与SFMC孵育后GABBR1表达水平降低。GABBR1与p38在RA关节中的表达取决于局部炎症，并且可以被糖皮质激素靶向。
