Suppression of autoimmune arthritis by Celastrus-derived Celastrol through modulation of pro-inflammatory chemokines.
Suppression of autoimmune arthritis by Celastrus-derived Celastrol through modulation of pro-inflammatory chemokines.
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DOI：
10.1016/j.bmc.2012.06.050
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发表时间：
2012-09-01
影响因子：
3.5
通讯作者：
Moudgil, Kamal D.
中科院分区：
文献类型：
--
作者：
Venkatesha, Shivaprasad H.;Astry, Brian;Nanjundaiah, Siddaraju M.;Yu, Hua;Moudgil, Kamal D.
关键词：
类风湿性关节炎（RA）是一种自身免疫性疾病，其特征是滑膜关节慢性炎症、畸形和残疾。长期使用传统的抗炎药物与严重的不良反应有关。因此，迫切需要更安全和更便宜的治疗产品。南蛇藤酚是中药南蛇藤的活性成分，具有抗关节炎的活性。然而，雷公藤红素的作用机制仍有待完全确定。在这项研究中，基于大鼠类风湿性关节炎（AA）模型，我们研究了雷公藤红素对关节炎炎症的两个关键介质，即趋化因子及其受体，以及相关的促炎细胞因子的影响。我们用雷公藤红素（200 μ g/大鼠）或其载体通过每日腹膜内（i.p.）在AA发作时开始注射。在AA高峰期，收集这些大鼠的血清、引流淋巴结细胞、脾粘附细胞和滑膜浸润细胞并进行检测。与溶剂处理的大鼠相比，雷公藤红素处理的大鼠显示趋化因子（RANTES、MCP-1、MIP-1 α和GRO/KC）以及诱导它们的细胞因子（TNF-α和IL-1 β）水平显著降低。然而，南蛇藤酚除了增加CCR1外，对趋化因子受体的细胞表达没有太大影响。此外，雷公藤红素在体外抑制脾贴壁细胞的迁移。因此，雷公藤红素诱导的抑制各种趋化因子介导细胞浸润到关节可能有助于其抗关节炎活性。我们的研究结果表明，雷公藤红素可能提供一个有前途的替代/辅助治疗类风湿关节炎
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints, deformities, and disability. The prolonged use of conventional anti-inflammatory drugs is associated with severe adverse effects. Therefore, there is an urgent need for safer and less expensive therapeutic products. Celastrol is a bioactive component of Celastrus, a traditional Chinese medicine, and it possesses anti-arthritic activity. However, the mechanism of action of Celastrol remains to be fully defined. In this study based on the rat adjuvant-induced arthritis (AA) model of RA, we examined the effect of Celastrol on two of the key mediators of arthritic inflammation, namely chemokines and their receptors, and related pro-inflammatory cytokines. We treated arthritic Lewis rats with Celastrol (200 μg/rat) or its vehicle by daily intraperitoneal (i.p.) injection beginning at the onset of AA. At the peak phase of AA, the sera, the draining lymph node cells, spleen adherent cells, and synovial-infiltrating cells of these rats were harvested and tested. Celastrol-treated rats showed a significant reduction in the levels of chemokines (RANTES, MCP-1, MIP-1α, and GRO/KC) as well as cytokines (TNF-α and IL-1β) that induce them, compared to the vehicle-treated rats. However, Celastrol did not have much effect on cellular expression of chemokine receptors except for an increase in CCR1. Further, Celastrol inhibited the migration of spleen adherent cells in vitro. Thus, Celastrol-induced suppression of various chemokines that mediate cellular infiltration into the joints might contribute to its anti-arthritic activity. Our results suggest that Celastrol might offer a promising alternative/adjunct treatment for RA
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影响因子：
15.3
作者：
Moudgil, K D;Chang, T T;Eradat, H;Chen, A M;Gupta, R S;Brahn, E;Sercarz, E E
通讯作者：
Sercarz, E E
影响因子：
4.4
作者：
Brodmerkel, CM;Huber, R;Vaddi, K
通讯作者：
Vaddi, K
DOI：
10.1073/pnas.96.8.4524
发表时间：
1999-04-13
影响因子：
11.1
作者：
Haqqi, TM;Anthony, DD;Mukhtar, H
通讯作者：
Mukhtar, H
影响因子：
15.9
作者：
Barnes, DA;Tse, J;Perez, HD
通讯作者：
Perez, HD
影响因子：
5.5
作者：
Marotte, Hubert;Ruth, Jeffrey H.;Ahmed, Salahuddin
通讯作者：
Ahmed, Salahuddin