Mackrell P J, Daly J M, Mestre J R, Stapleton P P, Howe L R, Subbaramaiah K, Dannenberg A J
Departments of Surgery, New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, NY10021, USA.
Surgery. 2001 Nov;130(5):826-33. doi: 10.1067/msy.2001.116669.
Cyclooxygenase-2 (Cox-2), the inducible form of Cox, is a rate-limiting enzyme in the synthesis of prostaglandins (PGs). Prostaglandin E2 (PGE2) and other eicosanoids possess immunosuppressive properties. Previously, traumatic injury was found to stimulate the synthesis of PGs and cause immune dysfunction. In this study a murine model was used to determine the effect of trauma on the expression of Cox-2 in macrophages and to elucidate the role of Cox-2 in trauma-induced immune dysfunction.
Mice were randomized to control or trauma (femur fracture plus 40% blood volume hemorrhage) groups. One, 4, and 7 days after injury, splenic macrophages were isolated and assayed for expression of Cox-2 and production of PGE2. In addition, the effect of pharmacologically inhibiting Cox-2 or knocking out the Cox-2 gene on trauma-induced suppression of splenocyte mitogenesis was determined.
Trauma led to increased expression of Cox-2, enhanced synthesis of PGE2, and suppressed splenocyte mitogenesis. Both pharmacologic inhibition and genetic deletion of Cox-2 abrogated trauma-mediated suppression of splenocyte mitogenesis.
These experiments link trauma-induced increases in Cox-2 expression and PGE2 production to reduced immune function. Cox-2 represents a potential pharmacologic target to prevent or reverse trauma-induced immunosuppression.
环氧化酶-2（Cox-2）是Cox的诱导型，是前列腺素（PGs）合成中的限速酶。前列腺素E2（PGE2）和其他类花生酸具有免疫抑制特性。此前发现创伤会刺激PGs的合成并导致免疫功能障碍。在本研究中，使用小鼠模型来确定创伤对巨噬细胞中Cox-2表达的影响，并阐明Cox-2在创伤诱导的免疫功能障碍中的作用。
将小鼠随机分为对照组或创伤组（股骨骨折加40%血容量出血）。在损伤后1天、4天和7天，分离脾巨噬细胞并检测Cox-2的表达和PGE2的产生。此外，还确定了药物抑制Cox-2或敲除Cox-2基因对创伤诱导的脾细胞有丝分裂抑制的影响。
创伤导致Cox-2表达增加、PGE2合成增强以及脾细胞有丝分裂受抑制。Cox-2的药物抑制和基因缺失均消除了创伤介导的脾细胞有丝分裂抑制。
这些实验将创伤诱导的Cox-2表达增加和PGE2产生与免疫功能降低联系起来。Cox-2是预防或逆转创伤诱导的免疫抑制的潜在药物靶点。
