Pharmacologic P2X Purinergic Receptor Antagonism in the Treatment of Collagen-Induced Arthritis
Pharmacologic P2X Purinergic Receptor Antagonism in the Treatment of Collagen-Induced Arthritis
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DOI：
10.1002/art.30556
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发表时间：
2011-11-01
影响因子：
--
通讯作者：
Traggiai, Elisabetta
中科院分区：
文献类型：
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作者：
Ardissone, Vittoria;Radaelli, Enrico;Traggiai, Elisabetta
客观的。评估 P2X 嘌呤能受体拮抗剂（即高碘酸氧化 ATP）在胶原诱导性关节炎 (CIA) 中的治疗潜力。方法。通过使用 II 型胶原蛋白 (CII) 进行免疫接种，在雄性 DBA/1J 小鼠中诱导关节炎。每天用100μl 3mM氧化ATP腹膜内治疗表现出手指炎症和爪肿胀的动物，持续10天。治疗期结束时，处死动物并取出爪子进行组织学分析和T细胞浸润评估。分析了对 CII 的体液反应，并将特定血清自身抗体水平与不同治疗组中观察到的临床评分相关。 结果。使用氧化 ATP 治疗可导致疾病活动持续降低，这与关节炎病变中 CD3+ T 细胞浸润的显着减少以及软骨侵蚀的显着改善有关。 P2X 阻断后，小鼠淋巴结中的外周 Treg 细胞显着增加。此外，检测到针对小鼠 CII 的循环自身抗体显着减少。血清自身抗体水平与氧化ATP临床疗效存在显着相关性。结论。我们的研究结果表明，P2X 受体拮抗作用在慢性炎症性风湿性疾病中具有重要的治疗潜力。总而言之，我们的结果强调了 P2X 受体信号通路作为 CIA 适应性免疫调节的潜在药理学靶点的价值。
Objective. To assess the therapeutic potential of a P2X purinergic receptor antagonist, namely, periodate oxidized ATP, in collagen-induced arthritis (CIA).Methods. Arthritis was induced in male DBA/1J mice by immunization with type II collagen (CII). Animals showing digit inflammation and paw swelling were treated intraperitoneally with 100 mu l of 3 mM oxidized ATP daily for 10 days. At the end of the treatment period, animals were killed and paws were removed for histologic analysis and evaluation of T cell infiltration. Humoral response to CII was analyzed, and specific serum autoantibody levels were correlated with the clinical scores observed in the different treatment groups.Results. Treatment with oxidized ATP resulted in a sustained reduction in disease activity, which was associated with a significant decrease in CD3+ T cell infiltration in arthritic lesions and a significant amelioration of cartilage erosion. Peripheral Treg cells were significantly increased upon P2X blockade in mouse lymph nodes. Moreover, a marked reduction in circulating autoantibodies directed against mouse CII was detected. There was a significant correlation between serum autoantibody levels and the clinical efficacy of oxidized ATP.Conclusion. Our findings indicate that P2X receptor antagonism has important therapeutic potential in chronic inflammatory rheumatic disorders. Taken together, our results underscore the value of the P2X receptor signaling pathway as a potential pharmacologic target for the modulation of adaptive immunity in CIA.