Suppression of acute rejection by administration of prostaglandin E2 receptor subtype 4 agonist in rat organ transplantation models.
Suppression of acute rejection by administration of prostaglandin E2 receptor subtype 4 agonist in rat organ transplantation models.
复制标题
在大鼠器官移植模型中施用前列腺素 E2 受体亚型 4 激动剂抑制急性排斥反应。
DOI：
10.1016/j.jss.2013.01.039
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
S. Uemoto
中科院分区：
文献类型：
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作者：
Tatsuya Okamoto;S. Okamoto;Y. Fujimoto;Y. Tabata;S. Uemoto
背景已知前列腺素 E2 (PGE2) 受体亚型 4 (EP4) 信号传导可调节炎症过程。多项研究已经证明 EP4 选择性激动剂在治疗自身免疫性疾病和炎症性疾病方面的潜在用途。在本研究中，我们评估了选择性EP4激动剂在实验性大鼠器官移植模型中的免疫抑制功效。方法我们通过皮下插入输液泵持续向接受异位心脏和小肠移植的受体大鼠注射选择性EP4激动剂（CAY10580）。结果EP4激动剂的给药显着 延迟了心脏同种异体移植物的存活并延迟了心脏和肠道同种异体移植物的排斥反应的发生。与媒介物治疗组相比，该治疗抑制了干扰素-γ促炎细胞因子的表达。此外，与对照组相比，细胞因子信号传导抑制因子-1（一种已知的 IFN-γ 细胞内调节因子）的表达也下调。结论这些结果表明，选择性 EP4 激动剂代表了一类新型免疫调节药物，可用于治疗急性同种异体排斥。
BackgroundProstaglandin E2(PGE2) receptor subtype 4 (EP4) signaling is known to modulate the inflammation process. Several studies have demonstrated the potential utility of EP4-selective agonists for the management of autoimmune and inflammatory diseases. In the present study, we assessed the immunosuppressive efficacy of a selective EP4 agonist in experimental rat organ transplantation models.MethodsWe continuously injected a selective EP4 agonist (CAY10580) by subcutaneous insertion of infuser pumps into recipient rats that underwent heterotopic heart and small bowel transplantation.ResultsThe administration of EP4 agonist significantly delayed cardiac allograft survival and delayed the onset of rejection in both the cardiac and intestinal allografts. Expression of proinflammatory cytokines of interferon-gamma was suppressed by the treatment compared with the vehicle-treated group. Furthermore, the expression of suppressor of cytokine signaling-1, a known intracellular regulation factor of IFN-gamma, was also down-regulated compared with the control group.ConclusionsThese results suggest that selective EP4 agonists represent a novel class of immune-modulator drugs that could be useful for the management of acute allogeneic rejection.