A high dose of ionizing radiation induces tissue-specific activation of nuclear factor-kappa B 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 io nizing 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 gamm a irradiation, the spleen, mesenteric lymph nodes, thymus, liver, lung, col on, brain and bone marrow were harvested 1, 2.5, 5, 10 and 20 h postirradia tion. NF-kappa B DNA-binding activity was analyzed in the nuclear protein e xtracts by a gel shift assay. When compared to the levels in untreated cont rol mice, radiation induced activation of NF-kappa B in spleen, mesenteric lymph nodes and bone marrow but not in the other tissues examined. In contr ast, an i.p. injection of a lethal dose (3 mg/kg) of lipopolysaccharide als o increased activity of NF-kappa B in the liver and lung. The gel supershif t assay with Nfkb1, Rela and/or Rel antibodies revealed that the specific m olecular forms of NF-kappa B activated by radiation in the spleen were Nfkb 1 homodimers and Nfkb1/Rela heterodimers. In mesenteric lymph nodes, the he terodimerized 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/Re la-like heterodimers, but it exhibited a higher mobility than Nfkb1 homodim ers, These results indicate that in vivo, ionizing radiation induces NF-kap pa B activation that varies in both tissue distribution and molecular compo sition. (C) 1999 by Radiation Research Society.