Synergy of IL-1 and Stem Cell Factor in Radioprotection of Mice is Associated with IL-1 Up-Regulation of mRNA and Protein Expression for c-kit on Bone Marrow Cells
ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
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Administration of IL-1 and stem cell factor SCF to mice 18 h before lethal 60 Co whole-body irradiation resulted in synergistic radioprotection, as evidenced by increased number of mice surviving 1,200 to 1,300 cGy doses of radiation and the recovery of increased number of c-kit bone marrow cells at 1 and 4 days after the lethal dose of 950 cGy. Anti-SCF Ab inhibited IL-1-induced radioprotection, indicating the endogenous production of SCE is necessary for radioprotection by IL-1. Conversely, radioprotection induced by SCF was reduced by Ant-IL-1R Ab, indicating that endogenous IL-1 contributes to SCF radioprotection. SCF, unlike IL-1, does not induce hemopoietic CSFs and IL-6 or gene expression of a scavenging mitochondrial enzyme manganese superoxide dismutase in the bone marrow, suggesting that SCF and IL-1 radioprotection by distinct pathways. The mRNA expression for c-kit by Northern blot analysis and 125 I-SCF binding on bone marrow cells was elevated with 2 and 4 h of Il-1 administration respectively. Four days after LD 10030 radiation the recovery of c-kit bone marrow cells was increased sixfold in IL-1-treated mice, almost 20- fold in SCF-treated mice, and 40-fold in mice treated with the combination of the two cytokines. Thus endogenous production of both IL-1 and SCF is required for resistance to lethal irradiation and the synergistic radioprotective effect of the two cytokines may, in part depend on IL-1 and SCF-induced increases in numbers of c-kit hemopoietic stem and progenitors cells that survive lethal irradiation.
- Anatomy and Physiology
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