Gamma irradiation-reduced IFN-gamma expression, STAT1 signals, and cell-mediated immunity

Abstract

The signal transducer and activator of transcription (STAT)1 is a cytoplasmic-transcription factor that is phosphorylated by Janus kinases (Jak) in response to interferon gamma(IFN-gamma). The phosphorylated STAT1 translocates to the nucleus, where it turns on specific sets of IFN-gamma-inducible genes, such as the interferon regulatory factor (IRF)-1. We show here that gamma irradiation reduces the IFN-gamma mRNA expression. The inhibition of the STAT1 phosphorylation and the IRF-1 expression by gamma irradiation was also observed. In contrast, the mRNA levels of IL-5 and transcription factor GATA-3 were slightly induced by gamma irradiation when compared to the non-irradiated sample. Furthermore, we detected the inhibition of cell-mediated immunity by gamma irradiation in the allogenic-mixed lymphocytes' reaction (MLR). These results postulate that gamma irradiation induces the polarized-Th2 response and interferes with STAT1 signals, thereby causing the immunosuppression of the Th1 response.