Tumor necrosis factor and interleukin-1 synergize with irradiation in expression of GM-CSF gene in human fibroblasts.
Tumor necrosis factor (TNF) and interleukin-1 (IL-1) improve the survival of lethally irradiated animals through production of hematopoietic growth factors. Exposure of fibroblasts to TNF (1000 U/ml) drastically increased granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA at 1 h and the level returned nearly to baseline by 24 h. Levels of GM-CSF RNA were less than basal level at 24 h after exposure to irradiation alone. In contrast, cells cultured with TNF (1 h) and then irradiated, had prominent expression of GM-CSF mRNA at 24 h. Transcriptional run-on analysis has shown that TNF stimulated the rate of GM-CSF transcription by > 10-fold in irradiated cells. Moreover, TNF stabilized GM-CSF mRNA at 24 h after irradiation; 4 increased from < 20 min in untreated cells to > 2 h in cells cultured initially with TNF and followed by irradiation. We repeated the same experiments with IL-1 and found that IL-1 had the same effects on accumulation, transcription, and stabilization of GM-CSF RNA. Our findings indicate that TNF and IL-1 synergize with irradiation in expression of GM-CSF gene in human fibroblasts; this increased expression occurs by enhancement of transcriptional rate and post-transcriptional stabilization of GM-CSF mRNA.
Hachiya
M
M
Division of Radiation Health, National Institute of Radiological Sciences, Chiba, Japan.
Koeffler
H P
HP
Suzuki
G
G
Akashi
M
M
D002478:Cells, Cultured; D004357:Drug Synergism; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D015870:Gene Expression / Q000528:radiation effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor