The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Caspase-8 as an Effector and Regulator of NLRP3 Inflammasome Signaling
Open accessAbstract
We recently described the induction of noncanonical IL-1β processing via caspase-8 recruited to ripoptosome signaling platforms in myeloid leukocytes. Here, we demonstrate that activated NLRP3·ASC inflammasomes recruit caspase-8 to drive IL-1β processing in murine bone marrow-derived dendritic cells (BMDC) independent of caspase-1 and -11. Sustained stimulation (>2 h) of LPS-primed caspase-1-deficient (Casp1/11(-/-)) BMDC with the canonical NLRP3 inflammasome agonist nigericin results in release of bioactive IL-1β in conjunction with robust caspase-8 activation. This IL-1β processing and caspase-8 activation do not proceed in Nlrp3(-/-) or Asc(-/-) BMDC and are suppressed by pharmacological inhibition of caspase-8, indicating that caspase-8 can act as a direct IL-1β-converting enzyme during NLRP3 inflammasome activation. In contrast to the rapid caspase-1-mediated death of wild type (WT) BMDC via NLRP3-dependent pyroptosis, nigericin-stimulated Casp1/11(-/-) BMDC exhibit markedly delayed cell death via NLRP3-dependent apoptosis. Biochemical analyses of WT and Casp1/11(-/-) BMDC indicated that caspase-8 is proteolytically processed within detergent-insoluble ASC-enriched protein complexes prior to extracellular export during nigericin treatment. Although nigericin-stimulated caspase-1 activation and activity are only modestly attenuated in caspase-8-deficient (Casp8(-/-)Rip3(-/-)) BMDC, these cells do not exhibit the rapid loss of viability of WT cells. These results support a contribution of caspase-8 to both IL-1β production and regulated death signaling via NLRP3 inflammasomes. In the absence of caspase-1, NLRP3 inflammasomes directly utilize caspase-8 as both a pro-apoptotic initiator and major IL-1β-converting protease. In the presence of caspase-1, caspase-8 acts as a positive modulator of the NLRP3-dependent caspase-1 signaling cascades that drive both IL-1β production and pyroptotic death.
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Citations
Cites
Activation and regulation of the inflammasomes
Latz, E., Xiao, T. S., & Stutz, A. (2013) · Nature Reviews Immunology · doi:10.1038/nri3452 · Cited by 2,884
Non-canonical inflammasome activation targets caspase-11
Kayagaki, N., Warming, S., Lamkanfi, M., Walle, L. V., Louie, S., Dong, J., Newton, K., Qu, Y., Liu, J., Heldens, S., et al. (2011) · Nature · doi:10.1038/nature10558 · Cited by 2,530
Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
Oberst, A., Dillon, C. P., Weinlich, R., McCormick, L. L., Fitzgerald, P., Pop, C., Hakem, R., Salvesen, G. S., & Green, D. R. (2011) · Nature · doi:10.1038/nature09852 · Cited by 1,278 · cited 1×
“Caspase-8knock-out mice are embryonic lethal due to unrestrained necroptosis and require co-deletion of RIP3 to rescue viability (7, 36).”
BackgroundRIP3 mediates the embryonic lethality of caspase-8-deficient mice
Kaiser, W. J., Upton, J. W., Long, A. B., Livingston-Rosanoff, D., Daley-Bauer, L. P., Hakem, R., Caspary, T., & Mocarski, E. S. (2011) · Nature · doi:10.1038/nature09857 · Cited by 1,057
Self-citationFernandes-Alnemri, T., Wu, J., Yu, J.-W., Datta, P., Miller, B., Jankowski, W., Rosenberg, S., Zhang, J., & Alnemri, E. S. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402194 · Cited by 1,026
Baroja-Mazo, A., Martín-Sánchez, F., Gomez, A. I., Martínez, C. M., Amores-Iniesta, J., Compan, V., Barberà-Cremades, M., Yagüe, J., Ruiz-Ortiz, E., Antón, J., et al. (2014) · Nature Immunology · doi:10.1038/ni.2919 · Cited by 790 · cited 4×
“An alternative mechanism for the delayed propidium2 uptake in Casp1/11 / DC AUGUST 14, 2015 • VOLUME 290 • NUMBER 33 JOURNAL OF BIOLOGICAL CHEMISTRY 20181 may involve a canonical caspase-8-driven apoptotic cascade that facilitates caspase-3-mediated proteolytic gating of pannexin-1 channels that are also expressed in…”
BackgroundInfluentialHildebrand, J. M., Tanzer, M. C., Lucet, I. S., Young, S. N., Spall, S. K., Sharma, P., Pierotti, C., Garnier, J.-M., Dobson, R. C. J., Webb, A. I., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408987111 · Cited by 598
Inhibitor of Apoptosis Proteins Limit RIP3 Kinase-Dependent Interleukin-1 Activation
Vince, J. E., Wong, W. W.-L., Gentle, I., Lawlor, K. E., Allam, R., O'Reilly, L., Mason, K., Gross, O., Ma, S., Guarda, G., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.01.012 · Cited by 491
Die another way – non-apoptotic mechanisms of cell death
Tait, S. W. G., Ichim, G., & Green, D. R. (2014) · Journal of Cell Science · doi:10.1242/jcs.093575 · Cited by 366 · cited 1×
“Given its ubiquitous expression, caspase-8 contributes to the apoptosis or necroptosis of myeloid leukocytes in diverse models of microbial infection or pro-inflammatory stress (67, 68).”
BackgroundKarki, R., Man, S. M., Malireddi, R. K. S., Gurung, P., Vogel, P., Lamkanfi, M., & Kanneganti, T.-D. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.01.006 · Cited by 272
Cited by
The NLRP3 inflammasome: molecular activation and regulation to therapeutics
Swanson, K. V., Deng, M., & Ting, J. P.-Y. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0165-0 · Cited by 4,884
NLRP3 inflammasome activation and cell death
Huang, Y., Xu, W., & Zhou, R. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-021-00740-6 · Cited by 1,527
Necroptosis in development, inflammation and disease
Weinlich, R., Oberst, A., Beere, H. M., & Green, D. R. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.149 · Cited by 1,016
Interleukin-1 Beta—A Friend or Foe in Malignancies?
Bent, R., Moll, L., Grabbe, S., & Bros, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082155 · Cited by 444
Inflammasome signaling and regulation of interleukin-1 family cytokines
Chan, A. H., & Schroder, K. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20190314 · Cited by 373
Metadata
- Authors
- Antonopoulos, C., Russo, H. M., El Sanadi, C., Martin, B. N., Li, X., Kaiser, W. J., Mocarski, E. S., & Dubyak, G. R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 290
- Issue
- 33
- Pages
- 20167-20184
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1813258042
- Cited by
- 229
- References
- 12
- FWCI
- 8.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Antonopoulos, C., Russo, H. M., El Sanadi, C., Martin, B. N., Li, X., Kaiser, W. J., Mocarski, E. S., & Dubyak, G. R. (2015). Caspase-8 as an Effector and Regulator of NLRP3 Inflammasome Signaling. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m115.652321
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