摘要
目的:通过研究环氧化酶2(Cyclooxygenase 2,Cox-2)抑制剂对卡介苗(Bacillus Calmette-Guerin,BCG)感染的人脐血源性树突状细胞分泌的Th1/Th2型细胞因子水平的影响,探讨其抗膀胱肿瘤效应及其潜在机制。方法:从人脐带血中分离得到单个核细胞,将其诱导培养为树突状细胞(Dendritic cell,DC)。采用BCG感染DC,并与前列腺素E_2(PGE_2)、塞来昔布等共培养,ELISA法检测各组培养上清中Th1型细胞因子IL-12和Th2型细胞因子IL-10表达水平。结果:经鉴定证实获得形态学及表型典型的DC。ELISA检测结果显示BCG可同时增加DC的IL-12和IL-10分泌,而塞来昔布剂量依赖性地显著增强BCG感染DC的IL-12的表达,抑制其IL-10表达;PGEE_2的作用与此相反,提示塞来昔布可诱导偏向Th1型而PGE_2可诱导偏向Th2型免疫应答的免疫漂移作用。结论:选择性Cox-2抑制剂塞来昔布能够增强BCG激活的Th1型免疫应答,抑制Th2型应答,诱导向Th1型应答漂移,从而增强BCG激活的抗肿瘤免疫效应。其机制可能是通过抑制Cox-2活性下调PGE_2的表达,从而遏制PGE_2诱导的IL-10的分泌及其对IL-12分泌的抑制作用。
Objective：To investigate the anti-bladder tumor effect and potential mechanism implicated of Cyclooxygenase 2 （Cox-2） inhibitors via impact on Thl/Th2 type cytokines secretion of BCG-infected human cord blood derived dendritic cells. Methods： Mononuclear cells were isolated from human cord blood and induced to differentiate to dendritic cells （DCs） in vitro. Then DCs were stimulated mature using BCG. DCs were co-cultured with different agents like PGE^2, celecoxib. Thl type cytokine IL-12 and Th2-type cytokine IL-10 were measured in culture supernatant of each group by enzyme linked immunosorbent assay （ELISA）. Results： Identification of DCs showed that the cultured cells were morphologyand phenotype-typical DCs. ELISA results demonstrated that after BCG infection, both IL-12 and IL 10 production of DC increased significantly compared with blank group, Celecoxib stimulated a dose dependent increased IL-12 and decreased IL-10 production, meanwhile PGE2 was on the contrary. The results indicated that Celecoxib induced Th response drift to Thl, meanwhile PGE2 induced a drift to Th2 type response. Conclusions： Selective Corn2 inhibitor Celecoxib can enhance BCG-activated Thl-type and suppress Th2 type immune response, induce Thl-polarized immunological drift and thus increase BCG-activated anti-bladder tumor effect, by mechanism of down regulating PGE2 expression through Cox-2 inhibi- tion, and inhibiting PGE^2 induced IL-10 secretion and its suppressive effect on IL-12 secretion.
出处
《临床泌尿外科杂志》
北大核心
2011年第5期385-388,共4页
Journal of Clinical Urology
关键词
膀胱肿瘤
环氧化酶2
卡介苗
树突状细胞
bladder neoplasm
cyclooxygenase 2
bacillus calmette-guerin
dendritic cell
