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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 effects of cyclooxygenase 2 (Cox-2) inhibitor on the level of Th1 / Th2 cytokines secreted by human umbilical cord blood-derived dendritic cells infected with Bacillus Calmette-Guerin (BCG) Influence, explore its anti-bladder tumor effect and its underlying mechanism. Methods: Mononuclear cells were isolated from human umbilical cord blood and induced to dendritic cells (DCs). DCs were infected with BCG and co-cultured with prostaglandin E_2 (PGE_2) and celecoxib. The expression of Th1 cytokines IL-12 and Th2 cytokines IL-10 in each group were detected by ELISA. Results: It was confirmed that morphologically and phenotypically typical DCs were obtained. The results of ELISA showed that BCG could increase the secretion of IL-12 and IL-10 in DC at the same time, while celecoxib significantly increased the expression of IL-12 and inhibited the expression of IL-10 in BCG-infected DC in a dose-dependent manner. The effect of PGEE_2 In contrast, it is suggested that celecoxib may induce a bias toward Th1 type and PGE2 may induce immune drift toward a Th2-type immune response. CONCLUSION: Celecoxib, a selective Cox-2 inhibitor, can enhance BCG-activated Th1-type immune response, inhibit Th2-type response and induce Th1-type response drift, thereby enhancing the anti-tumor immune effect of BCG activation. The mechanism may be through the inhibition of Cox-2 activity down PGE2 expression, thereby inhibiting PGE2-induced IL-10 secretion and its inhibition of IL-12 secretion.