FAS FAS LIGAND INTERACTION CONTRIBUTES TO UV-INDUCED APOPTOSIS IN HUMAN KERATINOCYTES/

Keratinocytes in human skin undergo apoptosis during various inflammat ory processes and after ultraviolet (UV) irradiation. To determine if keratinocyte apoptosis mag be mediated by the Fas/APO-1 receptor (CD95 ), a signal transduction pathway known to initiate programmed cell dea th of lymphocytes, we investigated Fas expression, modulation, and fun ction in keratinocytes. Keratinocytes constitutively expressed the 2.5 - and 1.9-kb Fas transcripts, as well as the 43-kDa Fas protein. Treat ment of interferon-gamma-stimulated keratinocytes with Fas agonistic a ntibody significantly promoted their cell death, indicating that Fas i n keratinocytes is functional. UV irradiation induced Fas mRNA express ion within 16 to 24 h and Fas protein within 24 h and through 48 h aft er irradiation. Furthermore, keratinocytes constitutively expressed Fa s ligand (Fast) mRNA and protein. UV irradiation induced Fast mRNA as early as 4 h after irradiation and elevated Fast mRNA levels mere main tained for at least 24 h postirradiation. Moreover, a Fast neutralizin g antibody significantly reduced W-induced apoptosis of IFN-gamma-trea ted keratinocytes. Our data strongly suggest that the Fas system contr ibutes to keratinocyte apoptosis in UV-irradiated human skin. (C) 1997 Academic Press.