ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Proapoptotic chemotherapeutic drugs induce noncanonical processing and release of IL-1β via caspase-8 in dendritic cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 116 citations in OpenAlex.
- Molecular switches in cell death: the interplay of apoptosis and pyroptosis in cancer.Cell communication and signaling : CCS · 2026Review
- Caspase-8-mediated CYLD cleavage boosts LPS-induced endotoxic shock.Cell death and differentiation · 2026Article
- Oridonin attenuates TLR4-driven inflammation and autophagy in LPS-stimulated enteric glial cells: anFrontiers in cellular neuroscience · 2026Article
- Exploring the potential link between human papillomavirus infection and coronary artery disease: a review of shared pathways and mechanisms.Molecular and cellular biochemistry · 2025Review
- Conventional Chemotherapy and Inflammation: What Is the Role of the Inflammasome in the Tumor Microenvironment?Biomedicines · 2025Review
- Adipose tissue IL-18 production is independent of caspase-1 and caspase-11.Immunity, inflammation and disease · 2024Article
- Reduced interleukin-18 secretion by human monocytic cells in response to infections with hyper-virulent Streptococcus pyogenes.Journal of biomedical science · 2024Article
- Targeting caspase-8: a new strategy for combating hepatocellular carcinoma.Frontiers in immunology · 2024Review
- Transcriptional Profiling of SARS-CoV-2-Infected Calu-3 Cells Reveals Immune-Related Signaling Pathways.Pathogens (Basel, Switzerland) · 2023Article
- Gasdermins and pyroptosis in the kidney.Nature reviews. Nephrology · 2023Review
- Mitochondria in reproduction.Clinical and experimental reproductive medicine · 2023Article
- Necroptosis: A Pathogenic Negotiator in Human Diseases.International journal of molecular sciences · 2022Review
- Inflammasome Contribution to the Activation of Th1, Th2, and Th17 Immune Responses.Frontiers in microbiology · 2022Review
- Interaction of Mycobacteria With Host Cell Inflammasomes.Frontiers in immunology · 2022Review
- Genetic targeting of Card19 is linked to disrupted NINJ1 expression, impaired cell lysis, and increased susceptibility to Yersinia infection.PLoS pathogens · 2021Article
- The ubiquitylation of IL-1β limits its cleavage by caspase-1 and targets it for proteasomal degradation.Nature communications · 2021Article
- Regulation of Caspase-8 Activity at the Crossroads of Pro-Inflammation and Anti-Inflammation.International journal of molecular sciences · 2021Review
- The role of caspase-8 in the tumor microenvironment of ovarian cancer.Cancer metastasis reviews · 2021Review
- TGR5 activation attenuates neuroinflammation via Pellino3 inhibition of caspase-8/NLRP3 after middle cerebral artery occlusion in rats.Journal of neuroinflammation · 2021Article
- Structure, Activation and Regulation of NLRP3 and AIM2 Inflammasomes.International journal of molecular sciences · 2021Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The identification of noncanonical (caspase-1-independent) pathways for IL-1β production has unveiled an intricate interplay between inflammatory and death-inducing signaling platforms. We found a heretofore unappreciated role for caspase-8 as a major pathway for IL-1β processing and release in murine bone marrow-derived dendritic cells (BMDC) costimulated with TLR4 agonists and proapoptotic chemotherapeutic agents such as doxorubicin (Dox) or staurosporine (STS). The ability of Dox to stimulate release of mature (17-kDa) IL-1β was nearly equivalent in wild-type (WT) BMDC, Casp1(-/-)Casp11(-/-) BMDC, WT BMDC treated with the caspase-1 inhibitor YVAD, and BMDC lacking the inflammasome regulators ASC, NLRP3, or NLRC4. Notably, Dox-induced production of mature IL-1β was temporally correlated with caspase-8 activation in WT cells and greatly suppressed in Casp8(-/-)Rip3(-/-) or Trif(-/-) BMDC, as well as in WT BMDC treated with the caspase-8 inhibitor, IETD. Similarly, STS stimulated robust IL-1β processing and release in Casp1(-/-)Casp11(-/-) BMDC that was IETD sensitive. These data suggest that TLR4 induces assembly of caspase-8-based signaling complexes that become licensed as IL-1β-converting enzymes in response to Dox and STS. The responses were temporally correlated with downregulation of cellular inhibitor of apoptosis protein 1, suggesting suppressive roles for this and likely other inhibitor of apoptosis proteins on the stability and/or proteolytic activity of the caspase-8 platforms. Thus, proapoptotic chemotherapeutic agents stimulate the caspase-8-mediated processing and release of IL-1β, implicating direct effects of such drugs on a noncanonical inflammatory cascade that may modulate immune responses in tumor microenvironments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.