TY - JOUR
T1 - Effects of NF-κB1 (p50) targeted gene disruption on ionizing radiation-induced NF-κB activation and TNFα, IL-1α, IL-1β and IL-6 mRNA expression in vivo
AU - Zhou, D.
AU - Yu, T.
AU - Chen, G.
AU - Brown, S. A.
AU - Yu, Z.
AU - Mattson, M. P.
AU - Thompson, J. S.
N1 - Funding Information:
The study was supported inpart by grants from the National Institutes of Health (MH50855and CA768,8the8Uni)evsityrof Kentucky Medical Center and the National Leukemia Research Association, Inc., to D.Z., and a Merit Review grant from the Veterans Administration to J.T.
PY - 2001
Y1 - 2001
N2 - Purpose: To investigate the role of the NF-κB1 (p50) gene in ionizing radiation (IR)-induced NF-κB activation and TNFα, IL-1α, IL-1β and IL-6 mRNA expression in vivo. Materials and methods: NF-κB activation was analysed by the gel shift/supershift assay and the levels of TNFα, IL-1α, IL-1β and IL-6 mRNA were measured using RNase protection assay (RPA). Various tissues from BALB/c, B6,129P-Nfkb1 (NF-κB1 or p50 gene knockout, p50-/-) and B6,129PF2 (wild-type, p50+/+) mice were analysed before or after exposure to a lethal dose (8.5 Gy) of total-body γ-irradiation. Results: Exposure of BALB/c mice to total-body IR selectively activated NF-κB in the spleen, mesenteric lymph nodes (LN) and bone marrow (BM). Gel supershift assay using polyclonal antibodies against NF-κB p50, p65 or c-Rel protein revealed that the NF-κB p50 subunit is a critical component of the NF-κB complexes activated by IR in vivo. Discretely augmented TNFα, IL-1α, IL-1β and IL-6 mRNA expression was found in the spleen, LN and BM after BALB/c mice received IR. However, mice lacking the p50 gene (p50-/-) showed a significant reduction in IR-induced activation of NF-κB and increases in TNFα, IL-1α, IL-1β and IL-6 mRNA expression, as compared with that of wild-type mice (p50+/+). Conclusions: The NF-κB p50 subunit is a critical component of the NF-κB complexes activated by IR and it plays an important role in mediating IR-induced TNFα, IL-1α, IL-1β and IL-6 mRNA expression in vivo.
AB - Purpose: To investigate the role of the NF-κB1 (p50) gene in ionizing radiation (IR)-induced NF-κB activation and TNFα, IL-1α, IL-1β and IL-6 mRNA expression in vivo. Materials and methods: NF-κB activation was analysed by the gel shift/supershift assay and the levels of TNFα, IL-1α, IL-1β and IL-6 mRNA were measured using RNase protection assay (RPA). Various tissues from BALB/c, B6,129P-Nfkb1 (NF-κB1 or p50 gene knockout, p50-/-) and B6,129PF2 (wild-type, p50+/+) mice were analysed before or after exposure to a lethal dose (8.5 Gy) of total-body γ-irradiation. Results: Exposure of BALB/c mice to total-body IR selectively activated NF-κB in the spleen, mesenteric lymph nodes (LN) and bone marrow (BM). Gel supershift assay using polyclonal antibodies against NF-κB p50, p65 or c-Rel protein revealed that the NF-κB p50 subunit is a critical component of the NF-κB complexes activated by IR in vivo. Discretely augmented TNFα, IL-1α, IL-1β and IL-6 mRNA expression was found in the spleen, LN and BM after BALB/c mice received IR. However, mice lacking the p50 gene (p50-/-) showed a significant reduction in IR-induced activation of NF-κB and increases in TNFα, IL-1α, IL-1β and IL-6 mRNA expression, as compared with that of wild-type mice (p50+/+). Conclusions: The NF-κB p50 subunit is a critical component of the NF-κB complexes activated by IR and it plays an important role in mediating IR-induced TNFα, IL-1α, IL-1β and IL-6 mRNA expression in vivo.
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U2 - 10.1080/09553000110050047
DO - 10.1080/09553000110050047
M3 - Article
C2 - 11454276
AN - SCOPUS:0034743275
SN - 0955-3002
VL - 77
SP - 763
EP - 772
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
IS - 7
ER -