IL-17 induces production of IL-6 and IL-8 in rheumatoid arthritis synovial fibroblasts via NF-kappaB- and PI3-kinase/Akt-dependent pathways.
IL-17 induces production of IL-6 and IL-8 in rheumatoid arthritis synovial fibroblasts via NF-kappaB- and PI3-kinase/Akt-dependent pathways.
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DOI：
10.1186/ar1038
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发表时间：
2004
影响因子：
4.9
通讯作者：
Kim HY
中科院分区：
文献类型：
--
作者：
Hwang SY;Kim JY;Kim KW;Park MK;Moon Y;Kim WU;Kim HY
类风湿性关节炎（RA）发病机制的最新研究表明，滑膜成纤维细胞和T细胞作为相互激活反馈中的动态伙伴，通过分泌相互刺激的细胞因子和趋化因子，参与关节炎症的永久化。在这项研究中，我们研究了IL-17的作用，一个主要的Th 1细胞因子产生的活化T细胞，在RA滑膜成纤维细胞的活化。IL-17受体（IL-17 R）和IL-17 RB（IL-17受体B）的转录本存在于RA患者的成纤维细胞样滑膜细胞（FLS）中。IL-17 R在用IL-17体外刺激后以增加的表达应答，而IL-17 RB的水平没有变化。如前所述，IL-17增强了FLS中IL-6和IL-8的产生，但不影响IL-15的合成。IL-17似乎是比IL-15更强的IL-6和IL-8的诱导剂，并且在RA FLS中甚至产生与IL-1β相当的活化。IL-17介导的IL-6和IL-8的诱导通过激活磷脂酰肌醇3-激酶/Akt和NF-κB转导，而CD 40连接和p38 MAPK（丝裂原活化蛋白激酶）不太可能参与该过程。总之，这些结果表明，IL-17能够在RA FLS的激活中发挥更多的辅助作用，并为在关节炎炎症的治疗调节中靶向IL-17相关途径提供了基础。
Recent studies of the pathogenesis of rheumatoid arthritis (RA) have revealed that both synovial fibroblasts and T cells participate in the perpetuation of joint inflammation as dynamic partners in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other. In this study, we investigated the role of IL-17, a major Th1 cytokine produced by activated T cells, in the activation of RA synovial fibroblasts. Transcripts of IL-17R (IL-17 receptor) and IL-17RB (IL-17 receptor B) were present in fibroblast-like synoviocytes (FLS) of RA patients. IL-17R responded with increased expression upon in vitro stimulation with IL-17, while the level of IL-17RB did not change. IL-17 enhanced the production of IL-6 and IL-8 in FLS, as previously shown, but did not affect the synthesis of IL-15. IL-17 appears to be a stronger inducer of IL-6 and IL-8 than IL-15, and even exerted activation comparable to that of IL-1β in RA FLS. IL-17-mediated induction of IL-6 and IL-8 was transduced via activation of phosphatidylinositol 3-kinase/Akt and NF-κB, while CD40 ligation and p38 MAPK (mitogen-activated protein kinase) are not likely to partake in the process. Together these results suggest that IL-17 is capable of more than accessory roles in the activation of RA FLS and provide grounds for targeting IL-17-associated pathways in therapeutic modulation of arthritis inflammation.
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在已建立的II型胶原蛋白诱导的关节炎中，全身性白介素4治疗对软骨和骨骼破坏的保护。
DOI：
10.1186/ar14
发表时间：
1999
期刊：
Arthritis research
影响因子：
--
作者：
Joosten, L A;Lubberts, E;Helsen, M M;Saxne, T;Coenen-de Roo , C J;Heinegard, D;van den Berg , W B
通讯作者：
van den Berg , W B
影响因子：
4.9
作者：
Kehlen A;Pachnio A;Thiele K;Langner J
通讯作者：
Langner J
影响因子：
4.4
作者：
Shimada, M;Andoh, A;Samba, T
通讯作者：
Samba, T
影响因子：
3.8
作者：
Cai, LP;Yin, JP;Filvaroff, EH
通讯作者：
Filvaroff, EH
影响因子：
4.8
作者：
Pietravalle, F;LecoanetHenchoz, S;Gauchat, JF
通讯作者：
Gauchat, JF