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-1β (IL-1β) gene was induced immediately after irradiation and was increased for 2 h thereafter. Dibutyryl cyclic AMP also caused a persistent expression of the IL-1β 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-1β 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-1β 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-1β without inducing c-fos expression. These results suggest that ionizing radiation elicits early expression of the IL-1β 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 γ rays also induced IL-1β 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-1β 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.