IMMEDIATE-EARLY, TRANSIENT INDUCTION OF THE INTERLEUKIN-1-BETA GENE IN MOUSE SPLEEN MACROPHAGES BY IONIZING-RADIATION

In murine spleen cells, x ray irradiation induces the expression of th e IL-1 beta gene at multiple phases of the peak time. We analyzed the immediate-early phase of IL-1 beta mRNA accumulation. To determine the lineage of cells that showed the immediate response to irradiation, n ormal spleen cells were analyzed by Northern blotting and in situ hybr idization after separation by magnetic antibodies against specific cel l-surface antigens. Although mast of the spleen macrophages continuous ly expressed a low level of IL-1 beta mRNA, a portion of the macrophag e population transiently accumulated large amounts of IL-1 beta messag e immediately after irradiation. A macrophage-like leukemia cell line that resembles these inducible macrophages was identified. A similar i mmediate-early and transient increase in the IL-1 beta mRNA level occu rred when cultured spleen cells were irradiated with a low dose (3 Gy) of x rays. In contrast, the x ray-inducible expression of the IL-1 be ta gene was immediate and continuous, not transient, in spleen cells f rom whole-body irradiated mice. Results of the run-on transcription as say and the determination of the decrease in the message using culture d spleen and macrophage-like leukemia cells indicated that x ray irrad iation appears to activate the transcription of the IL-1 beta gene and partially stabilize the message. The results show that the x ray-indu ced immediate-early accumulation of IL-1 beta mRNA is regulated at bot h the transcriptional and post-transcriptional levels in an as yet uni dentified population of spleen macrophages.