类风湿性关节炎与基质金属蛋白酶的研究进展

研究表明类风湿性关节炎（rheumatoid arthritis,RA）发病机制与感染、遗传、内分泌等因素有关，众多细胞因子参与其发病。主要病理改变为关节滑膜及周围结缔组织异常增生、关节软骨进行性破坏为主的慢性自身免疫性疾病。以滑膜村里层细胞增生、血管翳形成，单个核细胞浸润，进而软骨侵蚀和关节破坏为病理特征。金属基质蛋白酶（matrix metalloproteinases,MMPs）是近年发现的能够降解细胞外基质的一类蛋白质，它在组织塑型，细胞外基质逆转、伤口修复过程中起重要作用。MMP与RA相关性的研究将开拓RA发病机制及合理治疗的新领域。     

NF-κB在类风湿性关节炎中的作用及调控机制

正类风湿性关节炎(RA)是1种慢性、系统性自身免疫性疾病,可累及人体许多组织与器官,对关节的破坏尤为严重。主要病理特征为炎性细胞浸润、滑膜组织增生、血管生成、血管翳形成、软骨的破坏及骨的侵蚀。目前认为炎性反应介质的持续作用是RA病变加重的主要原因。NF-κB是1种影响广泛的转录因子,能促进多种基因转录和表达,与炎性反应、免疫应答     

类风湿性关节炎与基质金属蛋白酶的研究进展

研究表明类风湿性关节炎(rheumatoidarthritis,RA)发病机制与感染、遗传、内分泌等因素有关,众多细胞因子参与其发病。主要病理改变为关节滑膜及周围结缔组织异常增生、关节软骨进行性破坏为主的慢性自身免疫性疾病。以滑膜衬里层细胞增生、血管翳形成,单个核细胞浸润,进而软骨侵蚀和关节破坏为病理特征。金属基质蛋白酶(matrixmetalloproteinases,MMPs)是近年发现的能够降解细胞外基质的一类蛋白质。它在组织塑型,细胞外基质逆转、伤口修复过程中起重要作用。MMP与RA相关性的研究将开拓RA发病机制及合理治疗的新领域。     

白细胞介素17在类风湿关节炎发病中的作用

类风湿关节炎(rheumatoid arthritis,RA)是一种慢性、持续性、系统性的自身免疫性疾病,常引起关节的破坏和功能障碍.其病理特征主要是滑膜的过度增生、大量的炎细胞浸润、微血管新生、血管翳形成及软骨和骨组织的破坏.据统计,中国RA的患病率为0.3％.流行病学的调查结果显示,遗传和环境因素是RA病因学的主要方面.     

中性粒细胞在类风湿性关节炎中的作用

一、概述类风湿性关节炎(rheumatoid arthritis,RA)是一种慢性自身免疫性炎性疾病,以滑膜增生、关节破坏及关节外表现为特征。虽然病因尚不明确,但已知滑膜中性粒细胞、滑膜巨噬细胞、滑膜成纤维细胞、T细胞和B细胞均涉及RA的发病,T、B细胞及巨噬细胞浸润滑膜,形成不连续的淋巴样聚集,甚至有时滑膜中     

类风湿关节炎中医药治疗的文献分析研究

<正>类风湿关节炎(rheumatoid arthritis,RA)是一种病因不明的以对称性、慢性、进行性多关节炎为主要表现的慢性全身性自身免疫性疾病,其发病率、致残率均较高,严重危害人类健康[1]。其多见于女性,男女患病比例约为1∶3,我国大陆地区的患病率为0.20%～0.40%[2]。其基本病理改变为滑膜增生、衬里层增厚、多种炎性细胞浸润、血管翳形成及软骨与骨组织的破坏[3]。RA属中医学"痹症、顽痹、尪痹"范     

丝裂原激活蛋白激酶信号转导通路在类风湿关节炎中的研究进展

类风湿关节炎（rheumatoid arthritis,RA）是一种以关节滑膜炎症为显著特征的慢性自身免疫系统疾病，其发病机制复杂且尚未完全阐明。多种细胞、细胞因子以及细胞间信号转导通路都参与了RA的发生发展，其中丝裂原激活蛋白激酶（mitogen activation protein kinase,MAPK）信号转导通路与RA发病关系紧密，在血管翳形成、滑膜炎症、骨破坏等过程中都发挥了重要作用。该文从MAPK信号通路在RA发病中与多种关键细胞、细胞因子的相互作用等方面，综述了MAPK信号转导通路在RA中的研究进展，以期为抗RA药物治疗研究提供方向和理论依据。     

白细胞介素-1、肿瘤坏死因子-α、滑膜细胞产生的转录因子核因子与类风湿性关节炎

类风湿性关节炎（RA）是一种慢性自身免疫性疾病,其基本的病理特征是滑膜增生伴关节软骨和骨组织的破坏。其中白细胞介素-1（IL-1）、肿瘤坏死因子-α（TNF-α）、滑膜细胞产生的转录因子核因子（NF—κB）在RA的发病和进程中起着关键作用。     

类风湿关节炎滑膜成纤维样细胞的蛋白质组学研究

目的研究类风湿关节炎(RA)和骨性关节炎(OA)关节滑膜成纤维样细胞(FLS)蛋白质组的表达差异,分析差异蛋白在RA关节滑膜增生中的作用。方法原代培养关节滑膜FLS,抽提细胞总蛋白并定量,通过高分辨双向电泳(2-DE)对RA和OA的滑膜FLS进行蛋白分离,找出其中表达差异的蛋白质点并进行质谱(MS)分析鉴定。结果 OA及RA滑膜FLS的2-DE图谱上分别显示有1324和1147个蛋白质点。其中47个蛋白质点在OA或RA滑膜FLS中有3倍以上的量变;12个蛋白质点只存在于OA滑膜FLS;15个蛋白质点只存在于RA滑膜FLS。选择54个蛋白质点进行MS,共成功鉴定34个蛋白质点。其中包括在OA中表达上升的人异天冬氨酸甲基转移酶(PIMT)和PIR(PIR),仅在RA中表达的硫氧还蛋白1(TRX-1)这三个与关节滑膜增生相关的蛋白质。结论 PIMT和PIR在RA中表达降低及TRX-1在RA中表达升高可能是RA关节滑膜增生,引起关节软骨破坏的原因之一。     

CC亚族趋化因子与类风湿关节炎研究进展

类风湿关节炎(Rheumatoid arthritis,RA)是一类以关节炎为主要临床表现的系统性自身免疫疾病,其基本病理特点是血管炎和滑膜炎.其主要特征是滑膜关节的炎症,导致进行性的软骨和软骨下骨的破坏,在关节内可以看到滑膜组织的异常增生、大量炎性细胞的浸润,如T细胞、B细胞和单核细胞,以及微血管数量的显著增加.     

Advancement in contemporary diagnostic and therapeutic approaches for rheumatoid arthritis

This review is intended to provide a summary of the pathogenesis, diagnosis and therapies for rheumatoid arthritis. Rheumatoid arthritis (RA) is a common form of inflammatory autoimmune disease with unknown aetiology. Bone degradation, cartilage and synovial destruction are three major pathways of RA pathology. Sentinel cells includes dendritic cells, macrophages and mast cells bound with the auto antigens and initiate the inflammation of the joints. Those cells further activates the immune cells on synovial membrane by releasing inflammatory cytokines Interleukin 1, 6, 17, etc., Diagnosis of this disease is a combinational approach comprises radiological imaging, blood and serology markers assessment. The treatment of RA still remain inadequate due to the lack of knowledge in disease development. Non-steroidal anti-inflammatory drugs, disease modifying anti rheumatic drugs and corticosteroid are the commercial drugs to reduce pain, swelling and suppressing several disease factors. Arthroscopy will be an useful method while severe degradation of joint tissues. Gene therapy is a major advancement in RA. Suppressor gene locus of inflammatory mediators and matrix degrading enzymes were inserted into the affected area to reduce the disease progression. To overcome the issues aroused from those therapies like side effects and expenses, phytocompounds have been investigated and certain compounds are proved for their anti-arthritic potential. Furthermore certain complementary alternative therapies like yoga, acupuncture, massage therapy and tai chi have also been proved for their capability in RA treatment.     

Stromelysin synthesizing cells in the synovial tissues of rheumatoid arthritis demonstrated by in situ hybridization and immunohistochemical methods

We identified the cells synthesizing stromelysin to be synovial cells in the synovial tissue from four biopsy cases with rheumatoid arthritis (RA) by in situ hybridization and immunohistochemical studies. In the cases which showed severe inflammation of synovia such as well developed lymphoid follicle and diffuse inflammatory infiltration, synovial cells located only in the superficial layer of synovial tissues showed abundant mRNA and enzymic protein of stromelysin.     

Increased binding of synovial T lymphocytes from rheumatoid arthritis to endothelial-leukocyte adhesion molecule-1 (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1).

The infiltration of the synovial membrane (SM) by mononuclear cells, mostly T cells, is a typical histopathological feature associated with rheumatoid arthritis (RA). The entry of T lymphocytes into the SM is believed to be mediated by a number of molecules in the endothelium that are induced in response to a series of inflammatory mediators. In this study, we have investigated the adhesion of synovial T cells from RA patients to two endothelial ligands: endothelial-leukocyte adhesion molecule-1 (ELAM-1), the only selectin known to function as a vascular addressin for T cells, and vascular cell adhesion molecule-1 (VCAM-1), the cellular ligand of VLA-4. Our results clearly demonstrate that synovial T cells isolated from both SM and synovial fluid (SF), bearing an activated and memory phenotype, displayed an enhanced capacity to interact with these two endothelial molecules as compared with T cells from peripheral blood (PB) either of the same RA patients or healthy donors. A further enhancement of VLA-4-mediated T cell binding to VCAM-1 and fibronectin could be observed when already in vivo-activated synovial T cells were stimulated in vitro with phorbol esters, suggesting the existence of several cellular affinity levels for both very late activation-4 (VLA-4) ligands. Moreover, both PB and synovial T cells from RA patients exhibited strong proliferative responses when they were cultured with either fibronectin or VCAM-1 in combination with submitogenic doses of anti-CD3 mAb. This increased endothelial binding ability of synovial T lymphocytes together with their proliferation in response to the interaction with VCAM-1 and fibronectin may represent important mechanisms in the regulation of T cell penetration and persistence in the chronically inflamed SM of RA.     

Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen.

Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw60). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on T cells obtained from synovial fluid and synovial membranes of patients with rheumatoid arthritis and other forms of inflammatory joint disease. The UM4D4 antigen is expressed at high surface density on about three-fourths of synovial fluid T cells and on a small subset of synovial fluid natural killer cells; in synovial tissue it is present on more than 90% of T cells in lymphoid aggregates, and on approximately 50% of T cells in stromal infiltrates In addition, UM4D4 is expressed in synovial tissue on a previously undescribed population of HLA-DR/DP-negative non-T cells with a dendritic morphology. Anti-UM4D4 was co-mitogenic for both RA and non-RA synovial fluid mononuclear cells, and induced IL-2 receptor expression. The UM4D4/CDw60 antigen may represent a functional activation pathway for synovial compartment T cells, which could play an important role in the pathogenesis of inflammatory arthritis.     

Intra-articular adenoviral-mediated gene transfer of trail induces apoptosis of arthritic rabbit synovium

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that primarily affects joints. In rheumatoid joints there is extensive synovial proliferation with diseased synovium becoming highly aggressive, attaching to the articular cartilage and bone to form what is termed a pannus. The formation of active pannus is central to erosive disease and resulting joint destruction. In this study, we examined the ability to eliminate the hyperplastic synovium by adenoviral-mediated gene transfer of human TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF family that is able to induce apoptosis through interaction with receptors containing death domains, DR4 and DR5. Infection of synovial cells derived from RA patients with Ad.TRAIL resulted in significant apoptosis in three out of five lines. Moreover, primary rabbit synovial fibroblasts were also sensitive to Ad.TRAIL-mediated gene transfer. In a rabbit model of arthritis, intra-articular gene transfer of TRAIL induced apoptosis in cells within the synovial lining, reduced leukocytic infiltration and stimulated new matrix synthesis by cartilage. These results demonstrate that TRAIL can affect the viability of the cells populating the activated synovium in arthritic joints and suggest that the delivery of TRAIL to arthritic joints may represent a non-invasive mechanism for inducing pannus regression.     

Interleukin 1 and tumor necrosis factor-alpha synergistically increase the production of interleukin 6 in human synovial fibroblast.

We have previously reported that synovial cells could participate in B cell differentiation processes in rheumatoid arthritis (RA) by producing interleukin-6 (IL-6) spontaneously or in response to interleukin-1 (IL-1) stimulation. In this paper, we examined the effects of tumor necrosis factor-alpha (TNF-alpha) on IL-6 production by human synovial fibroblasts. TNF-alpha, as well as IL-1, is a putative relevant molecule in the inflammatory process and in articular destruction in RA. Both IL-1 and TNF-alpha induced IL-6 production by synovial fibroblasts in a dose dependent manner. When synovial fibroblasts were stimulated by IL-1 and TNF-alpha in combination, IL-6 production increased synergistically after 48 hr of a 72 hr culture period. Kinetic studies revealed that the presence of both cytokines at the early phase of stimulation was required for the synergistic effect. These results suggest that TNF-alpha could be involved in a cytokine network in the affected joints of RA and could contribute synergistically with IL-1 to the IL-6 production by synovial fibroblasts in vivo.