Unknown

Dataset Information

0

Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1?, controlling necrosis-induced sterile inflammation.


ABSTRACT: Necrosis can induce profound inflammation or be clinically silent. However, the mechanisms underlying such tissue specificity are unknown. Interleukin-1? (IL-1?) 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-1? 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-1? inhibited its cytokine activity. In cell types exhibiting a silent necrotic phenotype, IL-1R2 remained associated with pro-IL-1?. 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-1?. Full IL-1? 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-1? activity postnecrosis and the mechanism allowing conditional release of this blockade.

SUBMITTER: Zheng Y 

PROVIDER: S-EPMC3659285 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1α, controlling necrosis-induced sterile inflammation.

Zheng Yue Y   Humphry Melanie M   Maguire Janet J JJ   Bennett Martin R MR   Clarke Murray C H MC  

Immunity 20130207 2


Necrosis can induce profound inflammation or be clinically silent. However, the mechanisms underlying such tissue specificity are unknown. Interleukin-1α (IL-1α) 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-1α activity is tightly controlled in a cell type-specific manner. Most cell types examined expressed a cytosolic IL-1 receptor 2 (IL-1R2  ...[more]

Similar Datasets

| S-EPMC5131011 | biostudies-literature
| S-EPMC3251090 | biostudies-other
| S-EPMC4051590 | biostudies-literature
| S-EPMC4423803 | biostudies-literature
| S-EPMC4303590 | biostudies-literature
2018-09-03 | PXD009174 | Pride
| S-EPMC3720827 | biostudies-literature
| S-EPMC3761642 | biostudies-literature
| S-EPMC5152572 | biostudies-literature
| S-EPMC10006084 | biostudies-literature