E-SELECTIN GENE INDUCTION BY IONIZING-RADIATION IS INDEPENDENT OF CYTOKINE INDUCTION

The mechanism of the x-ray-mediated inflammatory response in normal ti ssues is unknown. To determine whether leukocyte infiltration into irr adiated tissue is regulated by adhesion molecule expression, we quanti fied the synthesis of glycoproteins that participate in inflammation, We found that E-selectin is synthesized in a time-dependent manner fol lowing exposure to doses as low as 0.5 Gy, Northern blot analysis demo nstrated that E-selectin mRNA expression increased at 2 h after x-irra diation 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 fr om irradiated endothelial cells to the NFkB binding sequence from the E-selectin promoter, Nuclear protein binding to the NFkB binding seque nce was altered by antibodies to the p50 and p65 components of NFkB, T hese data demonstrate that E-selectin expression does not require cyto kine synthesis, but involves NFkB activation. (C) 1995 Academic Press, Inc.