Cellular origin of ionizing radiation-induced NF-kappaB activation in vivo and role of NF-kappaB in ionizing radiation-induced lymphocyte apoptosis.
OBJECTIVE
To investigate the cellular origin of ionizing radiation (IR)-induced NF-kappaB activation in vivo and the role of NF-kappaB in IR-induced lymphocyte apoptosis.


METHODS
NF-kappaB activities were analysed by gel shift/supershift assay in isolated murine T- and B-cells, macrophages (MPhi) 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 (DiOC(6)) uptake, annexin-V staining and the sub-G0/1 population, or by TUNEL assay.


RESULTS
The results showed that IR activated NF-kappaB in lymphocytes, including both T- and B-cells, but failed to do so in MPhi. Furthermore, T- and B-cell-deficient Rag1 mice exposed to IR exhibited a significant reduction in NF-kappaB activation as compared with normal mice. Although NF-kappaB1 (p50) gene knockout or NF-kappaB decoy oligonucleotide treatment specifically inhibited IR-induced lymphocyte NF-kappaB 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-kappaB activation in vivo. However, NF-kappaB activation has no significant effect on IR-induced lymphocyte apoptosis.
Meng
A
A
Division of Research, Department of Pathology and Laboratory Medicine Medical, University of South Carolina, Charleston, SC 29425, USA.
Yu
T
T
Chen
G
G
Brown
S A
SA
Wang
Y
Y
Thompson
J S
JS
Zhou
D
D
D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000528:radiation effects; D002232:Carbocyanines / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005456:Fluorescent Dyes / Q000494:pharmacology; D016193:G1 Phase / Q000528:radiation effects; D016654:Genes, RAG-1 / Q000235:genetics; D020287:In Situ Nick-End Labeling; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D009841:Oligonucleotides / Q000494:pharmacology; D011839:Radiation, Ionizing; D016192:Resting Phase, Cell Cycle / Q000528:radiation effects; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000528:radiation effects; D013997:Time Factors
D017304:Annexin A5; D002232:Carbocyanines; D005456:Fluorescent Dyes; D016328:NF-kappa B; D009841:Oligonucleotides; C007392:3,3'-dihexyl-2,2'-oxacarbocyanine