title: Induction of Fas ligand-mediated apoptosis by interferon-alpha.
abstract: Interferon-alpha (IFN-alpha) was among the first cytokines studied and the earliest to be used in clinical medicine for the treatment of viral infections and malignancies. Although the capacity of IFN-alpha to augment NK cell cytotoxicity against virus-infected target cells or tumor cells is well established, the mechanism has not been fully elucidated. Here we report that IFN-alpha stimulation of PBMC from healthy donors induces Fas (CD95) ligand (FasL) transcription and leads to increased cell surface FasL expression exclusively on the NK cell fraction. Furthermore, IFN-alpha augments the FasL-mediated cytotoxicity of normal PBMC against Fas-sensitive lymphoid tumor cells. In the context of innate immunity, induction of FasL by IFN-alpha can be viewed as an efficient mechanism to potentiate NK cell cytotoxicity in the presence of harmful targets, such as virally infected or transformed cells.
authors.affiliation: Department of Medicine, Hospital for Special Surgery and Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Kirou
authors.forename: R K
authors.initials: RK
authors.lastname: Vakkalanka
authors.forename: M J
authors.initials: MJ
authors.lastname: Butler
authors.forename: M K
authors.initials: MK
authors.lastname: Crow
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D053222:Fas Ligand Protein; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000737:chemistry; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008024:Ligands; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000097:blood
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016898:Interferon-alpha; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger