Fas/Fas ligand interaction contributes to UV-induced apoptosis in human keratinocytes

Abstract

Keratinocytes in human skin undergo apoptosis during various inflammatory processes and after ultraviolet (UV) irradiation. To determine if keratinocyte apoptosis may be mediated by the Fas/APO-1 receptor (CD95), a signal transduction pathway known to initiate programmed cell death of lymphocytes, we investigated Fas expression, modulation, and function in keratinocytes. Keratinocytes constitutively expressed the 2.5- and 1.9-kb Fas transcripts, as well as the 43-kDa Fas protein. Treatment of interferon- γ-stimulated keratinocytes with Fas agonistic antibody significantly promoted their cell death, indicating that Fas in keratinocytes is functional. UV irradiation induced Fas mRNA expression within 16 to 24 h and Fas protein within 24 h and through 48 h after irradiation. Furthermore, keratinocytes constitutively expressed Fas ligand (FasL) mRNA and protein. UV irradiation induced FasL mRNA as early as 4 h after irradiation andelevated FasL mRNA levels were maintained for at least 24 h postirradiation. Moreover, a FasL neutralizing antibody significantly reduced UV-induced apoptosis of IFN-γ-treated keratinocytes. Our data strongly suggest that the Fas system contributes to keratinocyte apoptosis in UV-irradiated human skin.