The mitochondrial apoptotic effectors BAX/BAK activate caspase-3 and -7 to trigger NLRP3 inflammasome and caspase-8 driven IL-1beta activation
Details
Publication Year 2018-11-27, Volume 25, Issue #9, Page 2339-2353 e4
Journal Title
Cell Reports
Publication Type
Journal Article
Abstract
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-1beta. Furthermore, BAX/BAK signaling induces a parallel pathway to NLRP3 inflammasome-mediated caspase-1-dependent IL-1beta 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-1beta maturation and secretion. Conversely, the pyroptotic cell death effectors gasdermin D and gasdermin E are not essential for BAX/BAK-induced IL-1beta 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-1beta activation is often associated with cellular stress, such as during chemotherapy.
Publisher
Cell Press
WEHI Research Division(s)
Inflammation; Cell Signalling And Cell Death; Systems Biology And Personalised Medicine; Molecular Genetics Of Cancer; Chemical Biology; Cancer And Haematology
PubMed ID
30485804
Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2018.10.103
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2018-12-18 02:54:33
Last Modified: 2018-12-18 04:07:50
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