The suppression of radiation-induced NF-kappaB activity by dexamethasone correlates with increased cell death in vivo.
In this study, we show that dexamethasone treatment increases ionizing radiation-induced cell death by inducing the inhibitory kappaBalpha (IkappaBalpha) pathway in mice. The effect of dexamethasone on radiation-induced cell death was assessed by changes in total spleen cellularity and bone marrow colony-forming unit-granulocyte-macrophage (CFU-GM) contents after total body irradiation. While in vivo treatment of mice with dexamethasone alone (1 mg/kg/day, for 2 days) failed to elicit cell death in spleen cells, the combined treatment with dexamethasone (1 mg/kg/day, for 2 days) and gamma-rays (1 or 5 Gy) caused a 50-80% reduction in total cellularity in spleen and CFU-GM contents in bone marrow. These results demonstrate that dexamethasone has a synergistic effect on radiation-induced cellular damages in vivo. Immunoblot analysis showed that dexamethasone treatment significantly increases IkappaBalpha expression in the spleens of irradiated mice. In addition, the dexamethasone treatment significantly reduced radiation-induced nuclear translocation of the nucleus factor-kappaB in the spleens of irradiated mice. These results indicate that dexamethasone treatment in vivo may increase radiation-induced cell damages by increasing IkappaBalpha expression in hematopoietic organs such as spleen and bone marrow.
Nam
Seon Young
SY
Division of Radiation Effect Research, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Seoul 132-703, Republic of Korea.
Chung
Hee-Yong
HY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D011832:Radiation Injuries / Q000209:etiology / Q000378:metabolism*; D011836:Radiation Tolerance / Q000187:drug effects
D016328:NF-kappa B; D003907:Dexamethasone