Adiponectin mitigates the severity of arthritis in mice with collagen-induced arthritis
Adiponectin mitigates the severity of arthritis in mice with collagen-induced arthritis
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DOI：
10.1080/03009740801910346
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发表时间：
2008-01-01
影响因子：
2.1
通讯作者：
Lee, S-K
中科院分区：
文献类型：
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作者：
Lee, S-W;Kim, J-H;Lee, S-K
目的：脂联素（Adiponectin，AD）被认为是一种炎症调节因子.本研究采用胶原诱导的类风湿关节炎（CIA）小鼠模型和RA滑膜成纤维细胞（RASF）研究AD对RA的影响。除对照组外，所有小鼠均注射II型胶原。关节炎发生后，在左后腿关节内注射AD（AD治疗组）。使用关节炎评分和爪厚度测量关节炎的严重程度。通过苏木精/伊红（HE）染色对关节切片进行组织病理学评估。免疫组化法检测CIA小鼠肿瘤坏死因子（TNF）、白细胞介素（IL）-1、IL-6和基质金属蛋白酶（MMP）-3的表达。在全关节置换术期间，从四名RA患者中获得滑膜组织。从该组织建立RASF培养物。用AD预处理RASF，并用TNF或IL-1刺激RASF。TNF，IL-1，IL-6和MMP-3的生产测定酶联免疫吸附试验（ELISA）和逆转录聚合酶链反应（RT-PCR）。结果：AD能显著减轻CIA小鼠关节炎的严重程度和RA的病理组织学改变。AD组关节组织中TNF、IL-1和MMP-3表达降低，但IL-6表达增加。此外，AD降低了TNF、IL-1和MMP-3在刺激RASF中的表达，并增加了IL-6在IL-1刺激RASF中的表达。AD显著抑制IL-1诱导的RASF增殖，尽管增加IL-6的表达。结论：这些数据表明，AD可能发挥抗炎作用的病理生理RA。
Objective: Adiponectin (AD) is considered an inflammation modulator. In this study, we investigated the effect of AD on rheumatoid arthritis (RA) using a collagen-induced arthritis (CIA) mouse model and RA synovial fibroblasts (RASF).Methods: Fifteen DBA/1 mice were divided into three groups. All mice, except the control group, were injected with type II collagen. AD was intra-articularly injected in the left hind legs after arthritis development (the AD-treated group). The severity of the arthritis was measured using an arthritis score and paw thickness. A histopathological assessment of joint sections was performed by haematoxylin/eosin (HE) staining. Tumour necrosis factor (TNF)-, interleukin (IL)-1, IL-6, and matrix metalloproteinase (MMP)-3 expression was evaluated by immunohistochemical staining in the CIA mice. Synovial tissue was obtained from four RA patients during total joint replacement. RASF cultures were established from this tissue. RASF were pretreated with AD and stimulated by TNF or IL-1. TNF, IL-1, IL-6, and MMP-3 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). RASF proliferation was evaluated using the MTT assay.Results: AD significantly mitigated the severity of the arthritis and histopathological findings indicative of RA in CIA mice. TNF, IL-1, and MMP-3 expression decreased, but IL-6 expression in AD-treated joint tissues increased. Moreover, AD reduced TNF, IL-1, and MMP-3 expression in stimulated RASF and increased IL-6 expression in IL-1-stimulated RASF. AD significantly inhibited IL-1-induced RASF proliferation, despite increased IL-6 expression.Conclusion: These data suggest that AD may play an anti-inflammatory role in the pathophysiology of RA.