Necroptosis and Inflammation

Necroptosis is a regulated form of necrosis, with the dying cell rupturing and releasing intracellular components that can trigger an innate immune response. Toll-like receptor 3 and 4 agonists, tumor necrosis factor, certain viral infections, or the T cell receptor can trigger necroptosis if the ac...

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Bibliographic Details
Published in:Annual review of biochemistry 2016-06, Vol.85 (1), p.743-763
Main Authors: Newton, Kim, Manning, Gerard
Format: Article
Language:English
Subjects:
Animal diseases
Animals
Apoptosis
Caspase 8 - genetics
Caspase 8 - immunology
Gene Expression Profiling
Gene Expression Regulation
Humans
Immune response
Immunity, Innate
Inflammation
Kinases
MLKL
Necrosis - genetics
Necrosis - immunology
Necrosis - pathology
Protein Kinases - genetics
Protein Kinases - immunology
Receptor-Interacting Protein Serine-Threonine Kinases - genetics
Receptor-Interacting Protein Serine-Threonine Kinases - immunology
RIPK1
RIPK3
Signal Transduction
Toll-Like Receptor 3 - genetics
Toll-Like Receptor 3 - immunology
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - immunology
Viral infections
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Summary:Necroptosis is a regulated form of necrosis, with the dying cell rupturing and releasing intracellular components that can trigger an innate immune response. Toll-like receptor 3 and 4 agonists, tumor necrosis factor, certain viral infections, or the T cell receptor can trigger necroptosis if the activity of the protease caspase-8 is compromised. Necroptosis signaling is modulated by the kinase RIPK1 and requires the kinase RIPK3 and the pseudokinase MLKL. Either RIPK3 deficiency or RIPK1 inhibition confers resistance in various animal disease models, suggesting that inflammation caused by necroptosis contributes to tissue damage and that inhibitors of these kinases could have therapeutic potential. Recent studies have revealed unexpected complexity in the regulation of cell death programs by RIPK1 and RIPK3 with the possibility that necroptosis is but one mechanism by which these kinases promote inflammation.
ISSN:0066-4154
1545-4509
DOI:10.1146/annurev-biochem-060815-014830