cDNA microarray analysis of cyclosporin A (CsA)-treated human peripheral blood mononuclear cells reveal modulation of genes associated with apoptosis, cell-cycle regulation and DNA repair.
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.
Baião
Ana Maria T
AM
Department of Genetics and Evolution, Federal University of São Carlos (UFSCar), Sao Carlos, SP 13565-905, Brazil.
Wowk
Pryscilla F
PF
Sandrin-Garcia
Paula
P
Junta
Cristina Moraes
CM
Fachin
Ana Lúcia
AL
Mello
Stephano S
SS
Sakamoto-Hojo
Elza T
ET
Donadi
Eduardo A
EA
Passos
Geraldo A S
GA
D017209:Apoptosis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D016572:Cyclosporine / Q000494:pharmacology*; D004260:DNA Repair / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis
D016572:Cyclosporine