| First Author | Vince JE | Year | 2012 |
| Journal | Immunity | Volume | 36 |
| Issue | 2 | Pages | 215-27 |
| PubMed ID | 22365665 | Mgi Jnum | J:181625 |
| Mgi Id | MGI:5312161 | Doi | 10.1016/j.immuni.2012.01.012 |
| Citation | Vince JE, et al. (2012) Inhibitor of Apoptosis Proteins Limit RIP3 Kinase-Dependent Interleukin-1 Activation. Immunity 36(2):215-27 |
| abstractText | Interleukin-1beta (IL-1beta) is a potent inflammatory cytokine that is usually cleaved and activated by inflammasome-associated caspase-1. To determine whether IL-1beta activation is regulated by inhibitor of apoptosis (IAP) proteins, we treated macrophages with an IAP-antagonist "Smac mimetic" compound or genetically deleted the genes that encode the three IAP family members cIAP1, cIAP2, and XIAP. After Toll-like receptor priming, IAP inhibition triggered cleavage of IL-1beta that was mediated not only by the NLRP3-caspase-1 inflammasome, but also by caspase-8 in a caspase-1-independent manner. In the absence of IAPs, rapid and full generation of active IL-1beta by the NLRP3-caspase-1 inflammasome, or by caspase-8, required the kinase RIP3 and reactive oxygen species production. These results demonstrate that activation of the cell death-inducing ripoptosome platform and RIP3 can generate bioactive IL-1beta and implicate them as additional targets for the treatment of pathological IL-1-driven inflammatory responses. |
