TY - JOUR
T1 - Cellular origin of ionizing radiation-induced NF-κB activation in vivo and role of NF-κB in ionizing radiation-induced lymphocyte apoptosis
AU - Meng, A.
AU - Yu, T.
AU - Chen, G.
AU - Brown, S. A.
AU - Wang, Y.
AU - Thompson, J. S.
AU - Zhou, D.
N1 - Funding Information:
The study was supported in part by grants from the National Institutes of Health (R01-CA78688 and R01-CA86688) and the National Leukemia Research Association, Inc., to D. Z. and grants from the Veterans Administration to J. T. and S. B.
PY - 2003/11
Y1 - 2003/11
N2 - Purpose: To investigate the cellular origin of ionizing radiation (IR)-induced NF-κB activation in vivo and the role of NF-κB in IR-induced lymphocyte apoptosis. Materials and methods: NF-κB activities were analysed by gel shift/ supershift assay in isolated murine T- and B-cells, macrophages (Mφ) and tissues from normal and T- and B-cell-deficient Rag1 mice with or without exposure to IR. IR-induced lymphocyte apoptosis was determined by analysis of 3,3′-dihexyloxacarbocyanine iodide (D iOC6) uptake, annexin-V staining and the sub-G0/1 population, or by TUNEL assay. Results: The results showed that IR activated NF-κB in lymphocytes, including both T- and B-cells, but failed to do so in Mφ. Furthermore, T- and B-cell-deficient Rag1 mice exposed to IR exhibited a significant reduction in NF-κB activation as compared with normal mice. Although NF-κB1 (p50) gene knockout or NF-κB decoy oligonucleotide treatment specifically inhibited IR-induced lymphocyte NF-κB activation, they had no significant effect on IR-induced lymphocyte apoptosis. Conclusions: This finding suggests that lymphocytes are the main cellular origin of IR-induced NF-κB activation in vivo. However, NF-κB activation has no significant effect on IR-induced lymphocyte apoptosis.
AB - Purpose: To investigate the cellular origin of ionizing radiation (IR)-induced NF-κB activation in vivo and the role of NF-κB in IR-induced lymphocyte apoptosis. Materials and methods: NF-κB activities were analysed by gel shift/ supershift assay in isolated murine T- and B-cells, macrophages (Mφ) and tissues from normal and T- and B-cell-deficient Rag1 mice with or without exposure to IR. IR-induced lymphocyte apoptosis was determined by analysis of 3,3′-dihexyloxacarbocyanine iodide (D iOC6) uptake, annexin-V staining and the sub-G0/1 population, or by TUNEL assay. Results: The results showed that IR activated NF-κB in lymphocytes, including both T- and B-cells, but failed to do so in Mφ. Furthermore, T- and B-cell-deficient Rag1 mice exposed to IR exhibited a significant reduction in NF-κB activation as compared with normal mice. Although NF-κB1 (p50) gene knockout or NF-κB decoy oligonucleotide treatment specifically inhibited IR-induced lymphocyte NF-κB activation, they had no significant effect on IR-induced lymphocyte apoptosis. Conclusions: This finding suggests that lymphocytes are the main cellular origin of IR-induced NF-κB activation in vivo. However, NF-κB activation has no significant effect on IR-induced lymphocyte apoptosis.
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U2 - 10.1080/09553000310001622814
DO - 10.1080/09553000310001622814
M3 - Article
C2 - 14698954
AN - SCOPUS:0346057817
SN - 0955-3002
VL - 79
SP - 849
EP - 861
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
IS - 11
ER -