An antagonist of monocyte chemoattractant protein 1 (MCP-1) inhibits arthritis in the MRL-lpr mouse model.
An antagonist of monocyte chemoattractant protein 1 (MCP-1) inhibits arthritis in the MRL-lpr mouse model.
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DOI：
10.1084/jem.186.1.131
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发表时间：
1997-07-07
影响因子：
15.3
通讯作者：
ClarkLewis, I
中科院分区：
文献类型：
--
作者：
Gong, JH;Ratkay, LG;Waterfield, JD;ClarkLewis, I
人单核细胞趋化蛋白(MCP)-1的拮抗剂，由MCP-1(9-76)组成，已被鉴定并显示在体外抑制MCP-1的活性。为了验证这一假设，通过抑制内源性MCP-1，拮抗剂在体内具有抗炎活性，我们在MRL-LPR小鼠关节炎模型中检验了它的效果。这种菌株会自发发展成一种类似于人类类风湿性关节炎的慢性炎症性关节炎。每天注射拮抗剂MCP-1(9-76)，通过测量关节肿胀和关节组织病理学评估来监测，可以预防关节炎的发生。相比之下，接受本地MCP-1治疗的对照组关节炎症状有所改善，表明这种抑制作用是该拮抗剂特有的。在实验中，只有在疾病已经发展之后才给予拮抗剂，症状和组织病理学明显减少，尽管个体的反应程度不同。抑制疾病的机制尚不清楚，尽管结果表明，它可能比体外观察到的竞争抑制配体结合更复杂。单核细胞趋化蛋白-1拮抗剂在关节炎中的有益作用的证明表明，趋化因子受体拮抗剂可能在炎症性疾病中具有治疗应用。
An antagonist of human monocyte chemoattractant protein (MCP)-1, which consists of MCP-1(9-76), had previously been characterized and shown to inhibit MCP-1 activity in vitro. To test the hypothesis that, by inhibiting endogenous MCP-1, the antagonist has antiinflammatory activity in vivo, we examined its effect in the MRL-lpr mouse model of arthritis. This strain spontaneously develops a chronic inflammatory arthritis that is similar to human rheumatoid arthritis. Daily injection of the antagonist, MCP-1(9-76), prevented the onset of arthritis as monitored by measuring joint swelling and by histopathological evaluation of the joints. In contrast, controls treated with native MCP-1 had enhanced arthritis symptoms, indicating that the inhibitory effect is specific to the antagonist. In experiments where the antagonist was given only after the disease had already developed, there was a marked reduction in symptoms and histopathology, although individuals varied in the magnitude of the response. The mechanism of inhibition of disease is not known, although the results suggest that it could be more complex than the competitive inhibition of ligand binding that is observed in vitro. The demonstration of the beneficial effects of an MCP-1 antagonist in arthritis suggests that chemokine receptor antagonists could have therapeutic application in inflammatory diseases.
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影响因子：
4.8
作者：
Kitaura, M;Nakajima, T;Yoshie, O
通讯作者：
Yoshie, O
DOI：
10.1073/pnas.91.9.3652
发表时间：
1994-04-26
影响因子：
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作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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