title: Regulation of apoptosis by type III interferons.
abstract: OBJECTIVE
  Two types of interferons (IFNs), type I (IFN-alpha/beta) and type III (IFN-lambdas), utilize distinct receptor complexes to induce similar signalling and biological activities, including recently demonstrated for IFN-lambdas antitumour activity. However, ability of type III IFNs to regulate cell population growth remains largely uncharacterized.
  
  
  METHODS
  Intact and modified human colorectal adenocarcinoma HT29 cells were used to study regulation of apoptosis by IFN-lambdas.
  
  
  CONCLUSIONS
  We report that the IFN-lambdaR1 chain of the type III IFN receptor complex possesses an intrinsic ability to trigger apoptosis in cells. Signalling induced through the intracellular domain of IFN-lambdaR1 resulted in G(1)/G(0) phase cell cycle arrest, phosphatidylserine surfacing and chromosomal DNA fragmentation. Caspase-3, caspase-8 and caspase-9 were activated; however, pancaspase inhibitor Z-VAD-FMK did not prevent apoptosis. In addition, the extent of apoptosis correlated with the level of receptor expression and was associated with prolonged IFN-lambda signalling. We also demonstrated that the ability to trigger apoptosis is a unique intrinsic function of all IFN receptors. However, more robust apoptosis was induced by signalling through type III IFN receptor than through type I or type II (IFN-gamma) receptors, suggesting higher cytotoxic potential of type III IFNs. In addition, we observed that IFN-gamma treatment sensitized HT29 cells to IFN-lambda-mediated apoptosis. These results provide evidence that type III IFNs, alone or in combination with other stimuli, have the potential to induce apoptosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, New Jersey Medical School-University Hospital Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, New Jersey Medical School-University Hospital Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lewis-Antes
authors.affiliation: Department of Biochemistry and Molecular Biology, New Jersey Medical School-University Hospital Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, New Jersey Medical School-University Hospital Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
authors.forename: M
authors.initials: M
authors.lastname: Balan
authors.affiliation: Department of Biochemistry and Molecular Biology, New Jersey Medical School-University Hospital Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Kotenko
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D010718:Phosphatidylserines; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D007372:Interferons; D020169:Caspases