Tham Sin Mun, Ng Kee Hui, Pook Sim Hwee, Esuvaranathan Kesavan, Mahendran Ratha
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 8, Singapore 119228.
Clin Dev Immunol. 2011;2011:865684. doi: 10.1155/2011/865684. Epub 2011 Oct 13.
The aim of this study was to monitor changes in the expression of immune-related genes in the bladder after tumor implantation. Mice were orthotopically implanted with MB49-PSA cells (C57BL/6 mice) on day 1 and terminated on days 7, 14, 21, and 28. Another mouse model (MBT-2/C3H mice) was examined at day 7. Gene expression analysis was performed using a TaqMan Low Density Mouse Immune Panel (Applied Biosystems, USA) on RNA extracted from the bladders. Selected genes were reconfirmed by real-time PCR analysis and RT-PCR on the mRNA from other animals. Immune suppressive (IL13, IL1β, PTGS2, NOS2, IL10, CTLA4, and CCL22) and immune stimulatory genes (CSF2, GZMB, IFNγ, CXCL10, TNFα, CD80, IL12a, and IL6) and AGTR2 were increased by day 7. By day 28, IL10, CCL2, CCL5, CXCL11, CTLA4, GZMB, IFNγ, CSF2, and IL6 were significantly increased. Therapeutic strategies involving TH1 induction and TH2 dampening may improve responses to immunotherapy.
本研究的目的是监测肿瘤植入后膀胱中免疫相关基因表达的变化。在第1天将MB49 - PSA细胞原位植入小鼠(C57BL / 6小鼠)体内,并在第7、14、21和28天处死。在第7天检查另一种小鼠模型(MBT - 2 / C3H小鼠)。使用TaqMan低密度小鼠免疫分析板(美国应用生物系统公司)对从膀胱中提取的RNA进行基因表达分析。通过实时PCR分析和对其他动物mRNA进行RT - PCR对选定基因进行再次确认。免疫抑制基因(IL13、IL1β、PTGS2、NOS2、IL10、CTLA4和CCL22)和免疫刺激基因(CSF2、GZMB、IFNγ、CXCL10、TNFα、CD80、IL12a和IL6)以及AGTR2在第7天时增加。到第28天,IL10、CCL2、CCL5、CXCL11、CTLA4、GZMB、IFNγ、CSF2和IL6显著增加。涉及诱导TH1和抑制TH2的治疗策略可能会改善对免疫疗法的反应。