Identification and characterization of the interferon-β-mediated p53 signal pathway in human peripheral blood mononuclear cells
2009
Zhang, Fanglin | Sriram, Subramaniam
The relationship between the p53 signal pathway and the response of human peripheral blood mononuclear cells (PBMC) to interferon (IFN)-β has hitherto not been examined. Using an oligonucleotide microarray, we found differential expression of at least 70 genes involved in the p53 signal pathway, including p53, which regulate cell proliferation and cell death following stimulation with IFN-β. We verified our observations on a limited set of p53-regulated genes at the transcriptional and translational levels. We also examined the consequences of the activation of the p53 signal pathway by IFN-β in PBMC. When cultured in the presence of T-cell mitogens, IFN-β restricted the entry of lymphocytes from the G0/G1 phase to the S phase and reduced the number of cells in the G2 phase. The addition of IFN-β alone did not increase apoptosis. However, in the presence of actinomycin D, a DNA-damaging agent, addition of IFN-β enhanced the susceptibility of PBMC to apoptosis. These observations suggest that, in spite of the activation of a number of mutually overlapping pathways mediating cell death, cell cycle arrest was the most evident consequence of IFN-β signalling in PBMC.
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