title: Type I interferons activate apoptosis in a Jurkat cell variant by caspase-dependent and independent mechanisms.
abstract: Although the antiviral actions of interferons (IFNs) are observed in most types of cells, the antiproliferative effects of IFNalpha/beta are variable as are the mechanisms of growth inhibition that may or may not be due to the induction of apoptosis. To understand more about the mechanisms that are responsible for IFNalpha/beta-stimulated apoptosis, we have characterized a new human Jurkat T cell variant named H123 where IFNalpha activates programmed cell death (PCD). No differences in IFNalpha-stimulated, Stat-dependent gene expression were detected between H123 cells and the parental Jurkat cells, which are growth inhibited, but do not undergo apoptosis with IFNalpha. Although IFNalpha stimulates the activity of both caspase 3 and 9 in H123 cells, the general caspase inhibitor Z-VAD only partially reverses the apoptotic actions of IFNalpha. Induction of apoptosis by IFNalpha occurs through a mitochondrial-dependent pathway in H123 cells, as demonstrated by the release of cytochrome C from the mitochondria. Furthermore, IFNalpha treatment of H123 cells stimulates the release of the serine protease HtrA2/Omi from the mitochondria, suggesting that it plays a role in the apoptotic actions of this cytokine. These results provide evidence for a novel type 1 IFN-mediated pathway that regulates apoptosis of T cells through a mitochondrial-dependent and caspase-dependent and independent pathway.
authors.affiliation: Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gamero
authors.forename: Ramesh
authors.initials: R
authors.lastname: Potla
authors.forename: Shuji
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Darren P
authors.initials: DP
authors.lastname: Baker
authors.forename: Robert
authors.initials: R
authors.lastname: Abraham
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Larner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein; D006131:Growth Inhibitors; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D019169:Jurkat Cells; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D012313:RNA / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D015843:Serpins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D061945:Caspase Inhibitors; C505533:FADD protein, human; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D006131:Growth Inhibitors; D016898:Interferon-alpha; D024101:Mitochondrial Proteins; D050791:STAT Transcription Factors; D015843:Serpins; D014764:Viral Proteins; D012313:RNA; D045304:Cytochromes c; C074641:interleukin-1beta-converting enzyme inhibitor; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2; C000615915:Htra2 protein, mouse; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases