Gamma irradiation-reduced IFN-gamma expression, STAT1 signals, and cell-mediated immunity.
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.
Han
Seon-Kyu
SK
Laboratory of Immunology, Korea Cancer Center Hospital, 215-4 Gongneung-dong, Nowon-ku, Seoul 139-706, Korea.
Song
Jie-Young
JY
Yun
Yeon-Sook
YS
Yi
Seh-Yoon
SY
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D050990:GATA3 Transcription Factor; D005720:Gamma Rays; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor; D013154:Spleen / Q000166:cytology / Q000528:radiation effects*; D018417:Th1 Cells; D015534:Trans-Activators / Q000096:biosynthesis* / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D050856:Interferon Regulatory Factor-1; D015848:Interleukin-5; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma