Induction of the expression of the interleukin-1 beta gene in mouse spleen by ionizing radiation.
Spleen cells freshly isolated from normal mice were irradiated with 20 Gy X rays in culture. Northern blot hybridizations revealed that expression of the interleukin-1 beta (IL-1 beta) gene was induced immediately after irradiation and was increased for 2 h thereafter. Dibutyryl cyclic AMP also caused a persistent expression of the IL-1 beta gene, although it differed from X rays in that it coincidentally induced expression of the c-fos gene, which was not induced by X rays. Activation of either protein kinase C or calmodulin also induced early expression of both IL-1 beta and c-fos. Myeloid cells collected from the spleen of mice with granulocytic leukemia were X-irradiated in culture as above. The leukemia cells responded to X rays as well as to other stimuli in the same manner as the spleen cells, except that IL-1 beta mRNA was no longer detected 30 min after irradiation while c-fos was detectable for 2 h. When the leukemia cells were irradiated twice with a 3-h interval between irradiations, the second irradiation led to prolonged expression of IL-1 beta without inducing c-fos expression. These results suggest that ionizing radiation elicits early expression of the IL-1 beta gene through a mechanism that does not involve protein kinase C or A, or the transcription factor, c-fos. Whole-body irradiation of mice with 50 Gy 137Cs gamma rays also induced IL-1 beta expression in spleen but not in bone marrow or liver, although there was a delay of several hours before it was amply expressed. Furthermore, a delay as long as 24 or 72 h was observed when the radiation dose was reduced to 8.5 or 4 Gy. The results of this in vivo study suggest that the rapidity of expression of the IL-1 beta gene is dependent on the dose of radiation, and that the cells in the body cannot respond to radiation as rapidly as cells in culture.
Ishihara
H
H
Division of Chemical Pharmacology, National Institute of Radiological Sciences, Chiba-shi, Japan.
Tsuneoka
K
K
Dimchev
A B
AB
Shikita
M
M
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology; D002588:Cesium Radioisotopes; D015870:Gene Expression; D016762:Genes, fos; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011493:Protein Kinase C / Q000378:metabolism; D011831:Radiation Genetics; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014916:Whole-Body Irradiation
D002147:Calmodulin; D002588:Cesium Radioisotopes; D007375:Interleukin-1; D003994:Bucladesine; D011493:Protein Kinase C