A high dose of ionizing radiation induces tissue-specific activation of nuclear factor-κB in vivo

Activation of the transcription factor nuclear factor-kappa B (NF-kappa B) is one of the important responses of cells to an external stress such as ionizing radiation. We studied radiation-nduced NP-kappa B activation in vivo in male BALB/c mice. After the mice were exposed to 8.5 Gy total-body gamma irradiation, the spleen, mesenteric lymph nodes, thymus, liver, lung, colon, brain and bone marrow were harvested 1, 2.5, 5, 10 and 20 h postirradiation. NF-kappa B DNA-binding activity was analyzed in the nuclear protein extracts by a gel shift assay. When compared to the levels in untreated control mice, radiation induced activation of NF-kappa B in spleen, mesenteric lymph nodes and bone marrow but not in the other tissues examined. In contrast, an i.p. injection of a lethal dose (3 mg/kg) of lipopolysaccharide also increased activity of NF-kappa B in the liver and lung. The gel supershift assay with Nfkb1, Rela and/or Rel antibodies revealed that the specific molecular forms of NF-kappa B activated by radiation in the spleen were Nfkb1 homodimers and Nfkb1/Rela heterodimers. In mesenteric lymph nodes, the heterodimerized Rel/Rela NF-kappa B was also activated. In bone marrow, an NF-kappa B-like binding factor was induced that may be Nfkb1/Rela- and Rel/Rela-like heterodimers, but it exhibited a higher mobility than Nfkb1 homodimers, These results indicate that in vivo, ionizing radiation induces NF-kappa B activation that varies in both tissue distribution and molecular composition. (C) 1999 by Radiation Research Society.