Ionizing radiation induces expression of interleukin 6 by human fibroblasts involving activation of nuclear factor-kappa B.

We here report that human lung fibroblasts respond to x-ray treatment (XRT) with release of interleukin (IL)-6. Synthesis of IL-6 upon ionizing radiation is preceded by an increase of IL-6 transcript levels resulting from transcriptional activation of the IL-6 gene. Analysis of deleted fragments of the IL-6 promoter indicated that transcriptional activation of the IL-6 promoter was due to enhanced binding activity of the transcription factor nuclear factor (NF)-kappa B. Although AP-1 did not participate in the rapid induction of the IL-6 promoter, its binding activity was also enhanced by XRT. In contrast to binding kinetics observed with NF-kappa B, AP-1 binding following XRT was biphasic with the second peak being dependent on de novo protein synthesis. In contrast, however, NF-IL-6 activity was not enhanced by XRT in fibroblasts. The introduction of both the NF-kappa B- and the AP-1 recognition sequence conferred inducibility by XRT to a heterologous promoter, with reporter gene activity being maximal 24 or 48 h following XRT, respectively. Sequential activation of two distinct transcription factors might thus contribute to synchronize transcriptional activation of different genes participating in the x-ray response.