TY - JOUR
T1 - E-selectin gene induction by ionizing radiation is independent of cytokine induction
AU - Hallahan, Dennis
AU - Clark, Elizabeth Talley
AU - Kuchibhotla, Jaya
AU - Gewertz, Bruce L.
AU - Collins, Tucker
PY - 1995/12/26
Y1 - 1995/12/26
N2 - The mechanism of the x-ray-mediated inflammatory response in normal tissues is unknown. To determine whether leukocyte infiltration into irradiated tissue is regulated by adhesion molecule expression, we quantified the synthesis of glycoproteins that participate in inflammation. We found that E-selectin is synthesized in a time-dependent manner following exposure to doses as low as 0.5 Gy. Northern blot analysis demonstrated that E-selectin mRNA expression increased at 2 h after x-irradiation and increased expression required no de novo protein synthesis. Transcription of the promoter region of E-selectin (-578 to +35) was transiently induced following x-irradiation, whereas deletion of the NFkB binding site eliminated x-ray induction. Electrophoretic mobility gel shift analysis confirmed increased binding of nuclear proteins from irradiated endothelial cells to the NFkB binding sequence from the E-selectin promoter. Nuclear protein binding to the NFkB binding sequence was altered by antibodies to the p50 and p65 components of NFkB. These data demonstrate that E-selectin expression does not require cytokine synthesis, but involves NFkB activation.
AB - The mechanism of the x-ray-mediated inflammatory response in normal tissues is unknown. To determine whether leukocyte infiltration into irradiated tissue is regulated by adhesion molecule expression, we quantified the synthesis of glycoproteins that participate in inflammation. We found that E-selectin is synthesized in a time-dependent manner following exposure to doses as low as 0.5 Gy. Northern blot analysis demonstrated that E-selectin mRNA expression increased at 2 h after x-irradiation and increased expression required no de novo protein synthesis. Transcription of the promoter region of E-selectin (-578 to +35) was transiently induced following x-irradiation, whereas deletion of the NFkB binding site eliminated x-ray induction. Electrophoretic mobility gel shift analysis confirmed increased binding of nuclear proteins from irradiated endothelial cells to the NFkB binding sequence from the E-selectin promoter. Nuclear protein binding to the NFkB binding sequence was altered by antibodies to the p50 and p65 components of NFkB. These data demonstrate that E-selectin expression does not require cytokine synthesis, but involves NFkB activation.
UR - http://www.scopus.com/inward/record.url?scp=0029561153&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1995.2841
DO - 10.1006/bbrc.1995.2841
M3 - Article
C2 - 8554599
AN - SCOPUS:0029561153
SN - 0006-291X
VL - 217
SP - 784
EP - 795
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -