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.
Division of Chemical Pharmacology, National Institute of Radiological Sciences, Chiba-shi, Japan.
H
H
Ishihara
K
K
Tsuneoka
A B
AB
Dimchev
M
M
Shikita
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