Baião Ana Maria T, Wowk Pryscilla F, Sandrin-Garcia Paula, Junta Cristina Moraes, Fachin Ana Lúcia, Mello Stephano S, Sakamoto-Hojo Elza T, Donadi Eduardo A, Passos Geraldo A S
Department of Genetics and Evolution, Federal University of São Carlos (UFSCar), Sao Carlos, SP 13565-905, Brazil.
Mol Cell Biochem. 2007 Oct;304(1-2):235-41. doi: 10.1007/s11010-007-9505-7. Epub 2007 May 30.
Cyclosporin A (CsA) is a potent immunosuppressant that has been extensively used to attenuate patient immune response following organ transplantation. The molecular biological mechanism of CsA has been extensively investigated in human T cells, and it has been shown to involve modulation of the intracellular calcineurin pathway. However, it is plausible that this chemical immunosuppressant certainly up- or down-regulate many other biochemical pathways of immune cells. In the present study, we used the cDNA microarray method to characterize the gene expression profile of human peripheral blood mononuclear cells (PBMC) treated in vitro with CsA and controls. The CsA treated PBMC displayed statistically significant induction of genes involved in the control of cell-cycle regulation (TRRAP), apoptosis/DNA repair (PRKDC, MAEA, TIA1), DNA metabolism/response to DNA damage stimulus (PRKDC, FEN1), transcription (NR4A2, THRA) and cell proliferation (FEN1, BIN1), whose data have permitted identification of target genes involved in CsA immunosuppression.
环孢素A(CsA)是一种强效免疫抑制剂,已被广泛用于减轻器官移植后患者的免疫反应。CsA的分子生物学机制已在人类T细胞中进行了广泛研究,结果表明它涉及细胞内钙调神经磷酸酶途径的调节。然而,这种化学免疫抑制剂肯定会上调或下调免疫细胞的许多其他生化途径,这是合理的。在本研究中,我们使用cDNA微阵列方法来表征体外经CsA处理的人外周血单个核细胞(PBMC)和对照的基因表达谱。经CsA处理的PBMC在参与细胞周期调控(TRRAP)、凋亡/DNA修复(PRKDC、MAEA、TIA1)、DNA代谢/对DNA损伤刺激的反应(PRKDC、FEN1)、转录(NR4A2、THRA)和细胞增殖(FEN1、BIN1)控制的基因方面表现出统计学上显著的诱导,这些数据有助于识别参与CsA免疫抑制的靶基因。