The Mechanism of Anti-Inflammatory Effects of Prostaglandin E2 Receptor 4 Activation in Murine Cardiac Transplantation
The Mechanism of Anti-Inflammatory Effects of Prostaglandin E2 Receptor 4 Activation in Murine Cardiac Transplantation
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DOI：
10.1097/tp.0b013e3181a5c84c
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发表时间：
2009-06-15
期刊：
影响因子：
6.2
通讯作者：
Isobe, Mitsuaki
中科院分区：
文献类型：
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作者：
Ogawa, Masahito;Suzuki, Jun-Ichi;Isobe, Mitsuaki
背景。前列腺素 E-2 (PGE(2)) 是炎症性疾病的发病机制； PGE(2)在抗炎和免疫抑制方面发挥着关键作用。 EP4 是一种 PGE(2) 受体，已知可在体外抑制炎症细胞因子和趋化因子的产生。尽管有报道EP4激动剂可延长心脏同种异体移植物的存活率，但其免疫学机制却很少被阐明。方法。我们将选择性 EP4 激动剂 (EP4RAG) 注射到异位心脏移植的受体小鼠中。结果。与媒介物治疗组相比，EP4RAG 显着延长了移植物的存活时间。尽管媒介物处理组显示出严重的心肌细胞浸润，但EP4RAG处理组在第7天减弱了发展。与媒介物处理组相比，EP4RAG抑制了各种促炎因子，如细胞因子、趋化因子、粘附分子和核因子-κB (NF-κB)。我们还证明EP4RAG抑制巨噬细胞的活化，但在体外对T淋巴细胞没有影响。与对照组相比，EP4RAG抑制了NF-κB的激活。结论。在心脏移植中，药理学选择性 EP4 激活通过抑制 NF-κ B 活性来抑制促炎因子的产生。
Background. Prostaglandin E-2 (PGE(2)) is a pathogenesis of inflammatory diseases; PGE(2) plays a key role in association of anti-inflammation and immune suppression. EP4, which is a PGE(2) receptor, is known to suppress the production of inflammatory cytokines and chemokines in vitro. Although it has been reported that EP4 agonists prolonged cardiac allograft survival, little has been elucidated the immunologic mechanism.Methods. We injected a selective EP4 agonist (EP4RAG) into recipient mice with heterotopic cardiac transplantation.Results. EP4RAG significantly prolonged the graft survival compared with the vehicle-treated group. Although the vehicle-treated group showed severe myocardial cell infiltration, the EP4RAG-treated group attenuated the development on day 7. EP4RAG suppressed various proinflammatory factors such as cytokines, chemokines, adhesion molecules, and nuclear factor-kappa B (NF-kappa B) compared with the vehicle-treated group. We also demonstrated that EP4RAG suppressed the activation of macrophages, but it did not affect to T lymphocytes in vitro. EP4RAG inhibited the activation of NF-kappa B compared with the control group.Conclusion. Pharmacological selective EP4 activation suppressed the production of proinflammatory factors by inhibition of NF-kappa B activity in cardiac transplantation.