The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
The Mitochondrial Apoptotic Effectors BAX/BAK Activate Caspase-3 and -7 to Trigger NLRP3 Inflammasome and Caspase-8 Driven IL-1β Activation
Open accessAbstract
Intrinsic apoptosis resulting from BAX/BAK-mediated mitochondrial membrane damage is regarded as immunologically silent. We show here that in macrophages, BAX/BAK activation results in inhibitor of apoptosis (IAP) protein degradation to promote caspase-8-mediated activation of IL-1β. Furthermore, BAX/BAK signaling induces a parallel pathway to NLRP3 inflammasome-mediated caspase-1-dependent IL-1β maturation that requires potassium efflux. Remarkably, following BAX/BAK activation, the apoptotic executioner caspases, caspase-3 and -7, act upstream of both caspase-8 and NLRP3-induced IL-1β maturation and secretion. Conversely, the pyroptotic cell death effectors gasdermin D and gasdermin E are not essential for BAX/BAK-induced IL-1β release. These findings highlight that innate immune cells undergoing BAX/BAK-mediated apoptosis have the capacity to generate pro-inflammatory signals and provide an explanation as to why IL-1β activation is often associated with cellular stress, such as during chemotherapy.
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Citations
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TNFR1 and TNFR2 in the Control of the Life and Death Balance of Macrophages
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Self-citation
Metadata
- Authors
- Vince, J. E., De Nardo, D., Gao, W., Vince, A. J., Hall, C., McArthur, K., Simpson, D., Vijayaraj, S., Lindqvist, L. M., Bouillet, P., Rizzacasa, M. A., Man, S. M., Silke, J., Masters, S. L., Lessene, G., Huang, D. C. S., Gray, D. H. D., Kile, B. T., Shao, F., & Lawlor, K. E.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 25
- Issue
- 9
- Pages
- 2339-2353.e4
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2902287405
- Cited by
- 235
- References
- 22
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- gold
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