Identification and characterization of the interferon-beta-mediated p53 signal pathway in human peripheral blood mononuclear cells.
The relationship between the p53 signal pathway and the response of human peripheral blood mononuclear cells (PBMC) to interferon (IFN)-beta 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-beta. 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-beta in PBMC. When cultured in the presence of T-cell mitogens, IFN-beta 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-beta alone did not increase apoptosis. However, in the presence of actinomycin D, a DNA-damaging agent, addition of IFN-beta 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-beta signalling in PBMC.
Zhang
Fanglin
F
Department of Neurology, Multiple Sclerosis Research Center, Vanderbilt University Medical Center, Nashville, TN 37212, USA. Fanglin.zhang@vanderbilt.edu
Sriram
Subramaniam
S
D000328:Adult; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D050794:STAT1 Transcription Factor / Q000819:agonists / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D016159:Tumor Suppressor Protein p53; D016899:Interferon-beta