title: 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-gamma-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 and elevated FasL mRNA levels were maintained for at least 24 h postirradiation. Moreover, a FasL neutralizing antibody significantly reduced UV-induced apoptosis of IFN-gamma-treated keratinocytes. Our data strongly suggest that the Fas system contributes to keratinocyte apoptosis in UV-irradiated human skin.
authors.affiliation: Department of Dermatology, Boston University School of Medicine, Massachusetts 02118-2394, USA.
authors.forename: M
authors.initials: M
authors.lastname: Leverkus
authors.forename: M
authors.initials: M
authors.lastname: Yaar
authors.forename: B A
authors.initials: BA
authors.lastname: Gilchrest
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000528:radiation effects*; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000528:radiation effects; D014466:Ultraviolet Rays; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor; D007371:Interferon-gamma