IL-24 sensitizes tumor cells to TLR3-mediated apoptosis.
Cell Death Differ
; 20(6): 823-33, 2013 Jun.
Article
en En
| MEDLINE
| ID: mdl-23449395
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(IC), 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(IC), is associated with TLR3.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Interleucinas
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Apoptosis
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Receptor Toll-Like 3
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Viroterapia Oncolítica
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Neoplasias
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cell Death Differ
Año:
2013
Tipo del documento:
Article
País de afiliación:
Austria