IL-24 sensitizes tumor cells to TLR3-mediated apoptosis

R. Weiss, M. Sachet, J. Zinngrebe, T. Aschacher, M. Krainer, B. Hegedus, H. Walczak, M. Bergmann

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18 Citations (Scopus)

Abstract

Interleukin-24 (IL-24), a member of the IL-10 cytokine family whose physiological function remains largely unknown, has been shown to induce apoptosis when expressed in an adenoviral background. It is yet little understood, why IL-24 alone induced apoptosis only in a limited number of tumor cell lines. Analyzing an influenza A virus vector expressing IL-24 for its oncolytic potential revealed enhanced pro-apoptotic activity of the chimeric virus compared with virus or IL-24 alone. Interestingly, IL-24-mediated enhancement of influenza-A-induced apoptosis did not require viral replication but critically depended on toll-like receptor 3 (TLR3) and caspase-8. Immunoprecipitation of TLR3 showed that infection by influenza A virus induced formation of a TLR3-associated signaling complex containing TRIF, RIP1, FADD, cFLIP and pro-caspase-8. Co-administration of IL-24 decreased the presence of cFLIP in the TLR3-associated complex, converting it into an atypical, TLR3-associated death-inducing signaling complex (TLR3 DISC) that induced apoptosis by enabling caspase-8 activation at this complex. The sensitizing effect of IL-24 on TLR3-induced apoptosis, mediated by influenza A virus or the TLR3-specific agonist poly(I:C), was also evident on tumor spheroids. In conclusion, rather than acting as an apoptosis inducer itself, IL-24 sensitizes cancer cells to TLR-mediated apoptosis by enabling the formation of an atypical DISC which, in the case of influenza A virus or poly(I:C), is associated with TLR3.

Original languageEnglish
Pages (from-to)823-833
Number of pages11
JournalCell Death and Differentiation
Volume20
Issue number6
DOIs
Publication statusPublished - Jun 1 2013

Keywords

  • IL-24
  • TLR3
  • cancer
  • oncolytic influenza virus

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Weiss, R., Sachet, M., Zinngrebe, J., Aschacher, T., Krainer, M., Hegedus, B., Walczak, H., & Bergmann, M. (2013). IL-24 sensitizes tumor cells to TLR3-mediated apoptosis. Cell Death and Differentiation, 20(6), 823-833. https://doi.org/10.1038/cdd.2013.15