Effect of a CC chemokine receptor antagonist on collagen induced arthritis in DBA/1 mice
Effect of a CC chemokine receptor antagonist on collagen induced arthritis in DBA/1 mice
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DOI：
10.1016/s0165-2478(97)00075-8
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发表时间：
1997-06-01
影响因子：
4.4
通讯作者：
Wells, TNC
中科院分区：
文献类型：
--
作者：
PlaterZyberk, C;Hoogewerf, AJ;Wells, TNC
趋化因子是选择性激活白细胞并将其募集到炎症部位的小蛋白质。其中几种，包括CC趋化因子RANTES、MIP-1 α、MIP-1 β、MCP-1和CXC趋化因子IL-8、GRO-α、ENA-78，已在类风湿性滑膜中鉴定，暗示这些分子在类风湿性关节炎中的潜在作用。我们研究了CC趋化因子受体在胶原诱导的关节炎小鼠关节中的表达模式，胶原诱导的关节炎是人类类风湿性关节炎的模型。此外，我们研究了接受MetRANTES给药的小鼠关节炎的发病率和严重程度，MetRANTES是一种修饰的趋化因子，是某些CC趋化因子受体的纳摩尔拮抗剂。应用逆转录聚合酶链反应（RT-PCR）和原位杂交技术研究了关节炎小鼠关节中趋化因子及其受体的mRNA表达模式。与对照动物相比，在关节炎小鼠的关节中发现CC趋化因子受体mCCR 1、mCCR 2、mCCR 3和mCCR 5上调。此外，注射MetRANTES以剂量依赖性方式降低疾病的发生率。此外，与对照动物相比，在发生关节炎的MetRANTES治疗的小鼠中观察到疾病的严重程度显著降低。我们的数据清楚地表明CC趋化因子及其受体在炎性关节破坏中的作用，并支持使用趋化因子受体拮抗剂作为控制炎性疾病如类风湿性关节炎的潜在工具。(C)1997年Elsevier Science B.V.
Chemokines are small proteins that selectively activate and recruit leukocytes to sites of inflammation. Several of them, including the CC chemokines RANTES, MIP-1 alpha, MIP-1 beta, MCP-1, and the CXC chemokines IL-8, GRO-alpha, ENA-78 have been identified in rheumatoid synovium, implicating a potential role for these molecules in rheumatoid arthritis. We have investigated the expression patterns of CC chemokine receptors in the joints of mice with collagen-induced arthritis, a model for human rheumatoid arthritis. In addition, we have investigated the incidence and severity of arthritis in mice receiving administration of MetRANTES, a modified chemokine which is a nanomolar antagonist of certain CC chemokine receptors. The mRNA expression pattern of the chemokines and their receptors in the joints of arthritic mice was investigated using reverse transcriptase-PCR and in situ hybridization. An upregulation of the CC chemokine receptors mCCR1, mCCR2, mCCR3 and mCCR5 was found in the joints from arthritic mice, compared to control animals. In addition, injections of MetRANTES reduced the incidence of disease in a dose dependent manner. Furthermore, in MetRANTES-treated mice that did develop arthritis a significantly lower severity of disease was observed compared with control animals. Our data clearly demonstrate a role for CC chemokines and their receptors in inflammatory joint destruction and support the use of chemokine receptor antagonists as potential tools to control inflammatory diseases such as rheumatoid arthritis. (C) 1997 Elsevier Science B.V.