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.
Brach
M A
MA
Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Federal Republic of Germany.
Gruss
H J
HJ
Kaisho
T
T
Asano
Y
Y
Hirano
T
T
Herrmann
F
F
D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000528:radiation effects*; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000166:cytology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D014158:Transcription, Genetic
D015850:Interleukin-6; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D013006:Growth Hormone; D004247:DNA; D003513:Cycloheximide