IL-24 sensitizes tumor cells to TLR3-mediated apoptosis

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

Research output: Contribution to journalArticle

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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 2013

Fingerprint

Toll-Like Receptor 3
Apoptosis
Influenza A virus
Caspase 8
Neoplasms
Death Domain Receptor Signaling Adaptor Proteins
Viruses
interleukin-24
Tumor Cell Line
Immunoprecipitation
Interleukin-10
Human Influenza
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Weiss, R., Sachet, M., Zinngrebe, J., Aschacher, T., Krainer, M., Hegedűs, B., ... 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

IL-24 sensitizes tumor cells to TLR3-mediated apoptosis. / Weiss, R.; Sachet, M.; Zinngrebe, J.; Aschacher, T.; Krainer, M.; Hegedűs, B.; Walczak, H.; Bergmann, M.

In: Cell Death and Differentiation, Vol. 20, No. 6, 06.2013, p. 823-833.

Research output: Contribution to journalArticle

Weiss, R, Sachet, M, Zinngrebe, J, Aschacher, T, Krainer, M, Hegedűs, B, Walczak, H & Bergmann, M 2013, 'IL-24 sensitizes tumor cells to TLR3-mediated apoptosis', Cell Death and Differentiation, vol. 20, no. 6, pp. 823-833. https://doi.org/10.1038/cdd.2013.15
Weiss R, Sachet M, Zinngrebe J, Aschacher T, Krainer M, Hegedűs B et al. IL-24 sensitizes tumor cells to TLR3-mediated apoptosis. Cell Death and Differentiation. 2013 Jun;20(6):823-833. https://doi.org/10.1038/cdd.2013.15
Weiss, R. ; Sachet, M. ; Zinngrebe, J. ; Aschacher, T. ; Krainer, M. ; Hegedűs, B. ; Walczak, H. ; Bergmann, M. / IL-24 sensitizes tumor cells to TLR3-mediated apoptosis. In: Cell Death and Differentiation. 2013 ; Vol. 20, No. 6. pp. 823-833.
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