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J. Biol. Chem., Vol. 268, Issue 12, 8466-8472, Apr, 1993
MA Brach, HJ Gruss, T Kaisho, Y Asano, T Hirano and F Herrmann
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.
Ionizing radiation induces expression of interleukin 6 by human fibroblasts involving activation of nuclear factor-kappa B
Max-Delbruck-Centrum fur Molekulare Medizin, Berlin, Federal Republic of Germany.
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