Lories R J U, Derese I, Luyten F P, de Vlam K
Laboratory for Skeletal Development and Joint Disorders, Department of Rheumatology, University Hospitals Leuven, Catholic University Leuven, Belgium.
Clin Exp Rheumatol. 2008 Jan-Feb;26(1):96-102.
To study activation of intracellular pathways depending on nuclear factor kappa B (NFkappaB) and mitogen activated kinases (MAPK) in the synovium of patients with psoriatic arthritis before and after treatment with etanercept.
Synovial biopsies were obtained by needle arthroscopy of the knee in 9 patients with active psoriatic arthritis before the initiation of etanercept. Follow-up biopsies were taken in the same knee after 6 months. Synovitis was studied by histology. Pathway activation was studied by immunofluorescense for phosphorylated ERK, phosphorylated p38, phosphorylated JNK or phosphorylated inhibitor of kappa B (IkappaBalpha) using digital image analysis.
Histological severity scores were significantly reduced after etanercept treatment. Activation of NFkappaB signaling was found in the lining layer, and in infiltrating and peri-vascular cells in the sublining zone. Activated p38 was present in both lining and sublining layer. In the sublining layer, positive cells were found in inflammatory infiltrates, in perivascular zones and in the endothelium. Activated ERK was mainly present in the sublining layer, both in mononuclear cell infiltrates and perivascularly. Occasional positive cells were found in the lining layer. Activation of JNK was recognized in cells of the lining layer, in some of the sublining cell infiltrates and the perivascular compartment.
Etanercept therapy resulted in a significant decrease in NFkappaB, JNK and ERK, but not in p38 activation. Persistent activation of these pathways, albeit reduced, may trigger positive feedback loops and flares of arthritis after cessation of etanercept.
研究依那西普治疗前后银屑病关节炎患者滑膜中依赖核因子κB（NFκB）和丝裂原活化蛋白激酶（MAPK）的细胞内信号通路的激活情况。
对9例活动性银屑病关节炎患者在开始使用依那西普前，通过膝关节穿刺关节镜获取滑膜活检组织。6个月后在同一膝关节取随访活检组织。通过组织学研究滑膜炎。使用数字图像分析，通过对磷酸化细胞外信号调节激酶（ERK）、磷酸化p38、磷酸化c-Jun氨基末端激酶（JNK）或磷酸化κB抑制蛋白（IkappaBα）进行免疫荧光来研究信号通路激活情况。
依那西普治疗后组织学严重程度评分显著降低。在衬里层以及滑膜下层的浸润细胞和血管周围细胞中发现NFκB信号通路激活。活化的p38存在于衬里层和滑膜下层。在滑膜下层，炎症浸润、血管周围区域和内皮中发现阳性细胞。活化的ERK主要存在于滑膜下层，在单核细胞浸润处和血管周围均有。在衬里层偶尔发现阳性细胞。在衬里层细胞、一些滑膜下层细胞浸润和血管周围区域识别出JNK激活。
依那西普治疗导致NFκB、JNK和ERK激活显著降低，但p38激活未降低。这些信号通路的持续激活，尽管有所减弱，但可能在依那西普停用后触发正反馈回路和关节炎发作。
