Yang Yuan H, Morand Eric F, Getting Stephen J, Paul-Clark Mark, Liu Dong L, Yona Simon, Hannon Robert, Buckingham Julia C, Perretti Mauro, Flower Roderick J
Centre for Inflammatory Diseases, Monash University, Clayton, Victoria, Australia.
Arthritis Rheum. 2004 Mar;50(3):976-84. doi: 10.1002/art.20201.
Annexin 1 (Anx-1) is a putative mediator of the antiinflammatory actions of glucocorticoids (GCs). This study investigated the role of Anx-1 in experimental arthritis and in GC-mediated inhibition of inflammation, using antigen-induced arthritis (AIA) in Anx-1 knockout (Anx-1(-/-)) mice.
Arthritis was induced by intraarticular injection of methylated BSA (mBSA) in mice preimmunized with mBSA. Disease was assessed after 7 days by histologic examination of the knee joints. Serum levels of anti-mBSA IgG were determined by enzyme-linked immunosorbent assay. Cytokine messenger RNA (mRNA) expression was detected by real-time polymerase chain reaction.
A significant exacerbation of arthritis was observed in the Anx-1(-/-) mice compared with wild-type (WT) mice. This was associated with increased mRNA expression of synovial interleukin-1 beta, tumor necrosis factor alpha, interleukin-6, and macrophage migration inhibitory factor. Dexamethasone significantly reduced the histologic severity of synovitis and bone damage in the WT mice, but exerted no inhibitory effects in the Anx-1(-/-) mice, and also significantly reduced the serum levels of anti-mBSA IgG and the numbers of peripheral blood neutrophils and lymphocytes in WT mice, but had no such effect in Anx-1(-/-) mice.
Anx-1 exerts endogenous antiinflammatory effects on AIA via the regulation of cytokine gene expression, and also mediates the antiinflammatory actions of dexamethasone in AIA.
膜联蛋白1（Anx-1）被认为是糖皮质激素（GCs）抗炎作用的介质。本研究利用Anx-1基因敲除（Anx-1(-/-)）小鼠的抗原诱导性关节炎（AIA）模型，研究Anx-1在实验性关节炎及GC介导的炎症抑制中的作用。
用甲基化牛血清白蛋白（mBSA）对小鼠进行预免疫，然后通过关节腔内注射mBSA诱导关节炎。7天后通过膝关节组织学检查评估疾病情况。采用酶联免疫吸附测定法测定血清中抗mBSA IgG水平。通过实时聚合酶链反应检测细胞因子信使核糖核酸（mRNA）表达。
与野生型（WT）小鼠相比，Anx-1(-/-)小鼠的关节炎明显加重。这与滑膜白细胞介素-1β、肿瘤坏死因子α、白细胞介素-6和巨噬细胞移动抑制因子的mRNA表达增加有关。地塞米松显著降低了WT小鼠滑膜炎和骨损伤的组织学严重程度，但对Anx-1(-/-)小鼠没有抑制作用，地塞米松还显著降低了WT小鼠血清中抗mBSA IgG水平以及外周血中性粒细胞和淋巴细胞数量，但对Anx-1(-/-)小鼠没有这种作用。
Anx-1通过调节细胞因子基因表达对AIA发挥内源性抗炎作用，并且在AIA中介导地塞米松的抗炎作用。
