ArticleArthritis and rheumatism2009
Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta.
Article in Arthritis and rheumatism, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
159 citing papers in PubMed, 1 synthesis or guideline pooled it, 291 citations in OpenAlex.
- Interleukin-1 and Transforming Growth Factor Beta: Commonly Opposing, but Sometimes Supporting, Master Regulators of the Corneal Wound Healing Response to Injury.Investigative ophthalmology & visual science · 2021Pooled it
- Caspase-1 inhibition: mechanistic insights and comprehensive review of reported inhibitors to date.Inflammopharmacology · 2026Review
- Aluminum adjuvants differentially induce IL-1β release in vitro yet share NLRP3 inflammasome-independent adjuvant effects in vivo.Scientific reports · 2026Article
- Interaction Between Neutrophils and Elements of the Blood-Brain Barrier in the Context of Multiple Sclerosis and Ischemic Stroke.International journal of molecular sciences · 2025Review
- Anti-arthritis Effect of Anti-chitinase-3-like 1 Antibody Through Inhibition of MMP3.Immune network · 2025Article
- Triptolide attenuates LPS-induced chondrocyte inflammation by inhibiting inflammasome activation via the Wnt/β-catenin and NF-κB signaling pathways.Cytotechnology · 2025Article
- Sipeimine ameliorates osteoarthritis progression by suppression of NLRP3 inflammasome-mediated pyroptosis through inhibition of PI3K/AKT/NF-κB pathway: An in vitro and in vivo study.Journal of orthopaedic translation · 2024Article
- "How to Release or Not Release, That Is the Question." A Review of Interleukin-1 Cellular Release Mechanisms in Vascular Inflammation.Journal of the American Heart Association · 2024Review
- Pyroptosis by NLRP3/caspase-1/gasdermin-D pathway in synovial tissues of rheumatoid arthritis patients.Journal of cellular and molecular medicine · 2023Article
- Cathepsin B maturation plays a critical role in leptin-induced hepatic cancer cell growth through activation of NLRP3 inflammasomes.Archives of pharmacal research · 2023Article
- ASPS Exhibits Anti-Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ-Glutamylcysteine Level.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The regulation of self-tolerance and the role of inflammasome molecules.Frontiers in immunology · 2023Review
- Autoinflammatory manifestations in adult patients.Clinical and experimental immunology · 2022Article
- The IL-1 Family and Its Role in Atherosclerosis.International journal of molecular sciences · 2022Review
- Article
- Innate immune imprints in SARS-CoV-2 Omicron variant infection convalescents.Signal transduction and targeted therapy · 2022Article
- Innate immune mechanisms of mRNA vaccines.Immunity · 2022Review
- TREM-1 is required for enhanced OpZ-induced superoxide generation following priming.Journal of leukocyte biology · 2022Article
- Rectal microbiota are coupled with altered cytokine production capacity following community-acquired pneumonia hospitalization.iScience · 2022Article
- The Role of Inflammasomes in Osteoarthritis and Secondary Joint Degeneration Diseases.Life (Basel, Switzerland) · 2022Review
99 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
objectiveCaspase 1, a known cysteine protease, is a critical component of the inflammasome. Both caspase 1 and neutrophil serine proteases such as proteinase 3 (PR3) can process pro-interleukin-1beta (proIL-1beta), a crucial cytokine linked to the pathogenesis of rheumatoid arthritis. This study was undertaken to establish the relative importance of caspase 1 and serine proteases in mouse models of acute and chronic inflammatory arthritis.
methodsAcute and chronic arthritis were induced in caspase 1-/- mice, and the lack of caspase 1 was investigated for its effects on joint swelling, cartilage metabolism, and histopathologic features. In addition, caspase 1 activity was inhibited in mice lacking active cysteine proteases, and the effects of dual blockade of caspase 1 and serine proteases on arthritis severity and histopathologic features were evaluated.
resultsSurprisingly, caspase 1-/- mice, in a model of acute (neutrophil-dominated) arthritis, developed joint swelling to an extent similar to that in wild-type control mice. Joint fluid concentrations of bioactive IL-1beta were comparable in caspase 1-/- mice and controls. In contrast, induction of chronic arthritis (characterized by minimal numbers of neutrophils) in caspase 1-/- mice led to reduced joint inflammation and less cartilage damage, implying a caspase 1-dependent role in this process. In mice lacking neutrophil serine PR3, inhibition of caspase 1 activity resulted in decreased bioactive IL-1beta concentrations in the synovial tissue and less suppression of chondrocyte anabolic function. In addition, dual blockade of both PR3 and caspase 1 led to protection against cartilage and bone destruction.
conclusionCaspase 1 deficiency does not affect neutrophil-dominated joint inflammation, whereas in chronic arthritis, the lack of caspase 1 results in reduced joint inflammation and cartilage destruction. These findings suggest that inhibitors of caspase 1 are not able to interfere with the whole spectrum of IL-1beta production, and therefore such inhibitors may be of therapeutic value only in inflammatory conditions in which limited numbers of neutrophils are present.
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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.