Cholecystokinin octapeptide exerts its therapeutic effects on collagen-induced arthritis by suppressing both inflammatory and Th17 responses
Cholecystokinin octapeptide exerts its therapeutic effects on collagen-induced arthritis by suppressing both inflammatory and Th17 responses
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胆囊收缩素八肽通过抑制炎症和 Th17 反应对胶原诱导的关节炎发挥治疗作用
DOI：
10.1007/s00296-010-1476-4
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发表时间：
2011-10-01
影响因子：
4
通讯作者：
Yu, Feng
中科院分区：
文献类型：
--
作者：
Li, Qiaoxia;Cong, Bin;Yu, Feng
本研究的目的是评估胆囊收缩素八肽（CCK-8）对胶原性关节炎（CIA）的潜在治疗作用，CIA是一种公认的小鼠实验疾病模型，具有与人类类风湿关节炎（RA）相似的多种组织病理学特征。用鸡ⅱ型胶原蛋白（CII）免疫DBA/1J小鼠诱导CIA。不同剂量CCK-8每天腹腔注射1周。CCK-8剂量为5和10 nmol而不是1 nmol的小鼠表现出明显延迟的CIA发作，显著降低了关节炎的发病率和严重程度。CCK-8处理显著降低关节炎小鼠关节或滑膜细胞培养上清中细胞因子（IL-17、IL-23、IL-6和TNF-α）和趋化因子单核细胞趋化蛋白1的产生，升高IFN-γ和TGF-β水平。CCK-8处理小鼠的T细胞增殖明显减少，产生低水平的IL-17和高水平的IFN-γ和TGF-β。此外，CCK-8处理的小鼠血清中cii特异性IgG，特别是IgG2a水平低于对照组小鼠。这些结果表明CCK-8可以有效抑制CIA的炎症和Th17反应。CCK-8可能是类风湿关节炎的一种新的治疗方式。
The purpose of this study was to evaluate the potential therapeutic effect of cholecystokinin octapeptide (CCK-8) on collagen-induced arthritis (CIA), an accepted murine experimental disease model with diverse histopathological features similar to human rheumatoid arthritis (RA). CIA was induced in DBA/1J mice by immunization with chicken collagen type II (CII). CCK-8 at different doses was intraperitoneally administered daily for 1 week. Mice treated with CCK-8 at doses of 5 and 10 nmol but not 1 nmol displayed much delayed onset of CIA and significantly lower incidence and decreased severity of arthritis. CCK-8 treatment significantly reduced the production of cytokines (IL-17, IL-23, IL-6 and TNF-α) and chemokines monocyte chemoattractant protein 1 in the joints of arthritic mice or in synovial cell culture supernatant, and increased the levels of IFN-γ and TGF-β. T cells from CCK-8 treated mice proliferated much less, produced low level of IL-17 and high levels of IFN-γ and TGF-β. Moreover, CCK-8 treated mice showed lower levels of CII-specific IgG, particularly that of IgG2a, in sera than those from control mice. These results indicate that CCK-8 is effective in suppressing both inflammatory and Th17 responses in CIA. CCK-8 may represent a new therapeutic modality for rheumatoid arthritis.