| First Author | Takahashi K | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 8 | Pages | 4520-4 |
| PubMed ID | 16585540 | Mgi Jnum | J:131169 |
| Mgi Id | MGI:3773104 | Doi | 10.4049/jimmunol.176.8.4520 |
| Citation | Takahashi K, et al. (2006) Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded RNA. J Immunol 176(8):4520-4 |
| abstractText | Upon viral infection, host cells trigger antiviral immune responses by inducing type I IFN and inflammatory cytokines. dsRNA generated during viral replication is recognized by the cytoplasmic RNA helicases retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, which interact with an adaptor, IFN-beta promoter stimulator-1, to activate the transcription factors NF-kappaB and IFN regulatory factor 3. In this article we demonstrate that caspase-8 and caspase-10 are involved in these pathways. Both caspases were cleaved during dsRNA stimulation, and overexpression of a cleaved form of these caspases activated NF-kappaB. Knockdown of caspase-10 or caspase-8 in a human cell line resulted in the reduction of inflammatory cytokine production. Cells derived from caspase-8-deficient mice also showed reduced expression of inflammatory cytokines as well as NF-kappaB activation. Furthermore, the Fas-associated death domain protein interacted with these two caspases and IFN-beta promoter stimulator 1. These results indicate that caspase-8 and caspase-10 are essential components that mediate NF-kappaB-dependent inflammatory responses in antiviral signaling. |
