Regulation of apoptosis by type III interferons

W. Li, A. Lewis-Antes, J. Huang, M. Balan, S. V. Kotenko

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Objective: Two types of interferons (IFNs), type I (IFN-α/β) and type III (IFN-λs), utilize distinct receptor complexes to induce similar signalling and biological activities, including recently demonstrated for IFN-λs antitumour activity. However, ability of type III IFNs to regulate cell population growth remains largely uncharacterized.Materials and methods: Intact and modified human colorectal adenocarcinoma HT29 cells were used to study regulation of apoptosis by IFN-λs. Results and Conclusions: We report that the IFN-λR1 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-λR1 resulted in G 1/G0 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-λ 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-γ) receptors, suggesting higher cytotoxic potential of type III IFNs. In addition, we observed that IFN-γ treatment sensitized HT29 cells to IFN-λ-mediated apoptosis. These results provide evidence that type III IFNs, alone or in combination with other stimuli, have the potential to induce apoptosis.

Original languageEnglish (US)
Pages (from-to)960-979
Number of pages20
JournalCell Proliferation
Volume41
Issue number6
DOIs
StatePublished - Dec 2008

All Science Journal Classification (ASJC) codes

  • Cell Biology

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