Regulation of p53 expression in PBMC by beta Interferon in Multiple Sclerosis (94.21)

Abstract

Abstract Background: Beta Interferon (IFN) is a first line treatment in Multiple Sclerosis (MS); however its mechanism of action remains unclear. P53 is a key player in regulating apoptosis through the transcriptional activation of target genes. Previous studies showed an integration of beta IFN signaling with stabilization of p53 in murine cells. We examined the activation and stabilization of p53 in PBMC following in vitro culture with beta IFN, and in patients receiving beta IFN treatment. Methods: PBMC were isolated from 6 heath controls (HC) and 6 MS patients and then cultured with beta IFN. We also examined p53 expression in 7 MS patients receiving beta IFN-1b treatment. P53 expression in vitro and in vivo experiments was determined by real time RT-PCR, Western blotting and flow cytometry. Results: P53 expression increased in a dose and time dependant manner following culture with beta IFN. Flow cytometry studies showed increased stabilization of p53 in CD3+ T cells and monocytes. PBMC isolated from MS patients receiving beta IFN in vivo also showed the increase in p53 stabilization. However, the stabilization varied between patients receiving beta IFN: two patients showed no increase in p53; in the remaining five patients, the kinetics of p53 induction varied. Conclusion: Our studies show that p53 is vigorously induced in PBMC in vitro and following injection of drug in vivo. P53 expression induced was variable between patients receiving beta IFN. We suggest that p53 can potentially regulate the expansion of autoreactive cells that might contribute to the development and progression of MS. The study was supported by funds from Serono Inc