T Maeda1, C Hao, V A Tron. 1. Department of Laboratory Medicine and Pathology, Faculty of Medicine, 4B1 W.C. Mackenzie Health Science Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2R7.
Abstract
BACKGROUND: Several additional members of the tumor necrosis factor (TNF) receptor family were recently identified. The existence of such receptors, which may play distinct and unique regulatory roles, suggests that complex regulatory mechanisms are involved in apoptosis. OBJECTIVE: This study examines the expression of several members of the TNF receptor family in human keratinocytes exposed to ultraviolet B (UVB) irradiation. METHODS: Human keratinocytes were exposed to increasing doses of UVB, total RNA was harvested, and a quantitative RNase protection assay was performed. RESULTS: Decoy receptor-3 (DcR3), a nonfunctional receptor that binds to Fas ligand (FasL), was constitutively expressed at high level in keratinocytes but decreased rapidly in cells exposed to UVB. Decoy receptor-2 (DcR2), a nonfunctional receptor that binds to TNF-related apoptosis-inducing ligand (TRAIL)/APO-2L, showed the opposite expression pattern. DcR2 was undetectable in unirradiated keratinocytes and was markedly up-regulated after exposure to UVB. Although the response showed significant delays at higher UVB doses, the patterns observed for DcR3 and DcR2 were consistent in this set of experiments. CONCLUSION: We conclude that UVB regulates expression of these two TNF decoy receptors in keratinocytes. This pathway may represent a novel mechanism for regulation of apoptosis in the skin.
BACKGROUND: Several additional members of the tumor necrosis factor (TNF) receptor family were recently identified. The existence of such receptors, which may play distinct and unique regulatory roles, suggests that complex regulatory mechanisms are involved in apoptosis. OBJECTIVE: This study examines the expression of several members of the TNF receptor family in human keratinocytes exposed to ultraviolet B (UVB) irradiation. METHODS:Human keratinocytes were exposed to increasing doses of UVB, total RNA was harvested, and a quantitative RNase protection assay was performed. RESULTS:Decoy receptor-3 (DcR3), a nonfunctional receptor that binds to Fas ligand (FasL), was constitutively expressed at high level in keratinocytes but decreased rapidly in cells exposed to UVB. Decoy receptor-2 (DcR2), a nonfunctional receptor that binds to TNF-related apoptosis-inducing ligand (TRAIL)/APO-2L, showed the opposite expression pattern. DcR2 was undetectable in unirradiated keratinocytes and was markedly up-regulated after exposure to UVB. Although the response showed significant delays at higher UVB doses, the patterns observed for DcR3 and DcR2 were consistent in this set of experiments. CONCLUSION: We conclude that UVB regulates expression of these two TNF decoy receptors in keratinocytes. This pathway may represent a novel mechanism for regulation of apoptosis in the skin.