Lee S-W, Kim J-H, Park M-C, Park Y-B, Lee S-K
Division of Rheumatology, Department of Internal Medicine, Institute for Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul, South Korea.
Scand J Rheumatol. 2008 Jul-Aug;37(4):260-8. doi: 10.1080/03009740801910346.
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).
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 (H&E) staining. Tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, 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 TNFalpha or IL-1beta. TNFalpha, IL-1beta, 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.
AD significantly mitigated the severity of the arthritis and histopathological findings indicative of RA in CIA mice. TNFalpha, IL-1beta, and MMP-3 expression decreased, but IL-6 expression in AD-treated joint tissues increased. Moreover, AD reduced TNFalpha, IL-1beta, and MMP-3 expression in stimulated RASF and increased IL-6 expression in IL-1beta-stimulated RASF. AD significantly inhibited IL-1beta-induced RASF proliferation, despite increased IL-6 expression.
These data suggest that AD may play an anti-inflammatory role in the pathophysiology of RA.
脂联素（AD）被认为是一种炎症调节因子。在本研究中，我们使用胶原诱导性关节炎（CIA）小鼠模型和类风湿关节炎滑膜成纤维细胞（RASF）研究了AD对类风湿关节炎（RA）的影响。
将15只DBA/1小鼠分为三组。除对照组外，所有小鼠均注射II型胶原。关节炎发展后，在左后肢关节内注射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（H&E）染色对关节切片进行组织病理学评估。通过免疫组织化学染色评估CIA小鼠中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6和基质金属蛋白酶（MMP）-3的表达。在全关节置换期间从四名RA患者获取滑膜组织。从该组织建立RASF培养物。RASF用AD预处理并由TNFα或IL-1β刺激。通过酶联免疫吸附测定（ELISA）和逆转录聚合酶链反应（RT-PCR）测量TNFα、IL-1β、IL-6和MMP-3的产生。使用MTT法评估RASF增殖。
AD显著减轻了CIA小鼠中关节炎的严重程度以及指示RA的组织病理学表现。TNFα、IL-1β和MMP-3表达降低，但AD治疗的关节组织中IL-6表达增加。此外，AD降低了受刺激的RASF中TNFα、IL-1β和MMP-3的表达，并增加了IL-1β刺激的RASF中IL-6的表达。尽管IL-6表达增加，但AD显著抑制了IL-1β诱导的RASF增殖。
这些数据表明AD可能在RA的病理生理学中发挥抗炎作用。
