ArticleThe American journal of pathology2010
Proteasome inhibitors prevent caspase-1-mediated disease in rodents challenged with anthrax lethal toxin.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Role of the inflammasome in insulin resistance and type 2 diabetes mellitus.Frontiers in immunology · 2023Review
- Beclin1-driven autophagy modulates the inflammatory response of microglia via NLRP3.The EMBO journal · 2019Article
- Cancer associated fibroblasts have phenotypic and functional characteristics similar to the fibrocytes that represent a novel MDSC subset.Oncoimmunology · 2015Article
- Distinct cathepsins control necrotic cell death mediated by pyroptosis inducers and lysosome-destabilizing agents.Cell cycle (Georgetown, Tex.) · 2015Article
- Shigella IpaH7.8 E3 ubiquitin ligase targets glomulin and activates inflammasomes to demolish macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Platelet-activating factor contributes to Bacillus anthracis lethal toxin-associated damage.The Journal of biological chemistry · 2014Article
- Arsenic trioxide and other arsenical compounds inhibit the NLRP1, NLRP3, and NAIP5/NLRC4 inflammasomes.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Molecular determinants for a cardiovascular collapse in anthrax.Frontiers in bioscience (Elite edition) · 2014Review
- A proteolytic cascade controls lysosome rupture and necrotic cell death mediated by lysosome-destabilizing adjuvants.PloS one · 2014Article
- Role of lysosome rupture in controlling Nlrp3 signaling and necrotic cell death.Cell cycle (Georgetown, Tex.) · 2013Article
- Anthrax and the inflammasome.Microbes and infection · 2012Review
- Anthrax lethal factor activates K(+) channels to induce IL-1β secretion in macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- New developments in vaccines, inhibitors of anthrax toxins, and antibiotic therapeutics for Bacillus anthracis.Current medicinal chemistry · 2011Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
NOD-like receptors (NLRs) and caspase-1 are critical components of innate immunity, yet their over-activation has been linked to a long list of microbial and inflammatory diseases, including anthrax. The Bacillus anthracis lethal toxin (LT) has been shown to activate the NLR Nalp1b and caspase-1 and to induce many symptoms of the anthrax disease in susceptible murine strains. In this study we tested whether it is possible to prevent LT-mediated disease by pharmacological inhibition of caspase-1. We found that caspase-1 and proteasome inhibitors blocked LT-mediated caspase-1 activation and cytolysis of LT-sensitive (Fischer and Brown-Norway) rat macrophages. The proteasome inhibitor NPI-0052 also prevented disease progression and death in susceptible Fischer rats and increased survival in BALB/c mice after LT challenge. In addition, NPI-0052 blocked rapid disease progression and death in susceptible Fischer rats and BALB/c mice challenged with LT. In contrast, Lewis rats, which harbor LT-resistant macrophages, showed no signs of caspase-1 activation after LT injection and did not exhibit rapid disease progression. Taken together, our findings indicate that caspase-1 activation is critical for rapid disease progression in rodents challenged with LT. Our studies indicate that pharmacological inhibition of NLR signaling and caspase-1 can be used to treat inflammatory diseases.
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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.