COACTIVATION OF AP-1 ACTIVITY AND TGF-BETA-1 GENE-EXPRESSION IN THE STRESS-RESPONSE OF NORMAL SKIN CELLS TO IONIZING-RADIATION

Activation of the AP-1 transcription factor and TGF-beta 1 growth fact or by ionizing radiation was studied both in vivo in pig skin, and in vitro in human fibroblasts and keratinocytes, Three and 6h after irrad iation, the Fos and Jun proteins and their binding activity to an AP-1 consensus sequence were strongly induced by high doses of gamma-rays, c-Fos, c-Jun and JunB proteins were found to be present in gel-shift complexes by probing with specific antibodies, Both keratinocytes and fibroblasts exhibited heightened AP-1 activity following irradiation, As we previously found that TGF-beta 1 is involved in the development of skin lesions induced by radiation, TGF-beta 1 gene expression was a lso examined, Two and 6h after irradiation, the levels of TGF-beta 1 t ranscripts were increased in skin, By immunostaining, TGF-beta 1 prote in levels were found to be increased in fibroblasts, keratinocytes and endothelial cells, As promoter contains AP-1 binding sites, between A P-1 activity and TGF-beta 1 induction was addressed, The -365 TGF-beta 1 promoter fragment, which contains a high affinity AP-1 site, exhibi ted increased binding to Jun and Fos proteins following irradiation, T hese results suggest that stress-inducible TGF-beta 1 expression is me diated by the activation of AP-1 transcription factor.