Ionizing radiation induces IL-6-production by human fibroblasts involving activation of nuclear factor-κB

The authors report that human lung fibroblasts respond to X-ray treatment 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 revealed that transcriptional induction of the IL-6 promoter is due to enhanced binding activity of the transcription factor NF-kB. Although AP-1 does not participate in the rapid induction of the IL-6 promoter its binding activity is also enhanced upon XRT. In contrast to binding kinetics observed with NF-kB, AP-1 binding upon XRT. In contrast to binding kinetics observed with NF-kB- and the AP-1 recognition sequence, conferred inducibility by XRT to a heterologous promoter, with reporter gene activity being maximal 24 hours or 48 hours upon 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