| First Author | Zheng Y | Year | 2013 |
| Journal | Immunity | Volume | 38 |
| Issue | 2 | Pages | 285-95 |
| PubMed ID | 23395675 | Mgi Jnum | J:193599 |
| Mgi Id | MGI:5468848 | Doi | 10.1016/j.immuni.2013.01.008 |
| Citation | Zheng Y, et al. (2013) Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1alpha, controlling necrosis-induced sterile inflammation. Immunity 38(2):285-95 |
| abstractText | Necrosis can induce profound inflammation or be clinically silent. However, the mechanisms underlying such tissue specificity are unknown. Interleukin-1alpha (IL-1alpha) is a key danger signal released upon necrosis that exerts effects on both innate and adaptive immunity and is considered to be constitutively active. In contrast, we have shown that necrosis-induced IL-1alpha activity is tightly controlled in a cell type-specific manner. Most cell types examined expressed a cytosolic IL-1 receptor 2 (IL-1R2) whose binding to pro-IL-1alpha inhibited its cytokine activity. In cell types exhibiting a silent necrotic phenotype, IL-1R2 remained associated with pro-IL-1alpha. Cell types possessing inflammatory necrotic phenotypes either lacked IL-1R2 or had activated caspase-1 before necrosis, which degraded and dissociated IL-1R2 from pro-IL-1alpha. Full IL-1alpha activity required cleavage by calpain after necrosis, which increased its affinity for IL-1 receptor 1. Thus, we report a cell type-dependent process that fundamentally governs IL-1alpha activity postnecrosis and the mechanism allowing conditional release of this blockade. |
