ArticleThe Journal of biological chemistry2009
Interleukin-33 is biologically active independently of caspase-1 cleavage.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 245 citations in OpenAlex.
- Targeting IL-33 in Precision Neuroimmunology: Cellular Mechanisms and Therapeutic Strategies for CNS Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Review
- Interleukin-33 at the intersection of inflammation and repair.Frontiers in allergy · 2026Review
- Pyroptosis: A spoiler of peaceful coexistence between cells in degenerative bone and joint diseases.Journal of advanced research · 2025Review
- A neutrophil elastase-generated mature form of IL-33 is a potent regulator of endothelial cell activation and proliferative retinopathy.Experimental & molecular medicine · 2024Article
- Interleukins IL33/ST2 and IL1-β in Intrauterine Growth Restriction and Seropositivity of Anti-Microorganisms · 2024Article
- Unpacking the complexity of nuclear IL-33 (nIL-33): a crucial regulator of transcription and signal transduction.Journal of cell communication and signaling · 2023Review
- IL-33 Expression Is Lower in Current Smokers at both Transcriptomic and Protein Levels.American journal of respiratory and critical care medicine · 2023Article
- Decoding the IL-33/ST2 Axis: Its Impact on the Immune Landscape of Breast Cancer.International journal of molecular sciences · 2023Review
- The Role of IL-33/ST2 in COPD and Its Future as an Antibody Therapy.International journal of molecular sciences · 2023Review
- Full-length IL-33 augments pulmonary fibrosis in an ST2- and Th2-independent, non-transcriptomic fashion.Cellular immunology · 2023Article
- Role of inflammasome in severe, steroid-resistant asthma.Current research in immunology · 2023Review
- Emerging Effects of IL-33 on COVID-19.International journal of molecular sciences · 2022Review
- Serum levels and single nucleotide polymorphisms of the interleukin-33 gene in atopic dermatitis.Postepy dermatologii i alergologii · 2022Article
- Inflammasomes and the IL-1 Family in Bone Homeostasis and Disease.Current osteoporosis reports · 2022Review
- Hepatic pannexin-1 mediates ST2Clinical and translational medicine · 2022Article
- Diverse Control Mechanisms of the Interleukin-1 Cytokine Family.Frontiers in cell and developmental biology · 2022Review
- Review
- Could Interleukin-33 (IL-33) Govern the Outcome of an Equine Influenza Virus Infection? Learning from Other Species.Viruses · 2021Review
- The Paradigm Change of IL-33 in Vascular Biology.International journal of molecular sciences · 2021Review
- Caspase-11 regulates lung inflammation in response to house dust mites.Cellular immunology · 2021Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The new interleukin (IL)-1 family cytokine IL-33 is synthesized as a 30-kDa precursor. Like pro-IL-1beta, human pro-IL-33 was reported to be cleaved by caspase-1 to generate an 18-kDa fragment, which is sufficient to activate signaling by the IL-33 receptor T1/ST2. However, the proposed caspase-1 cleavage site is poorly conserved between species. In addition, it is not clear whether caspase-1 cleavage of pro-IL-33 occurs in vivo and whether, as for IL-1beta, this cleavage is a prerequisite for IL-33 secretion and bioactivity. In this study, we further investigated caspase-1 cleavage of mouse and human pro-IL-33 and assessed the potential bioactivity of the IL-33 precursor. We observed the generation of a 20-kDa IL-33 fragment in cell lysates, which was enhanced by incubation with caspase-1. However, in vitro assays of mouse and human pro-IL-33 indicated that IL-33 is not a direct substrate for this enzyme. Consistently, caspase-1 activation in THP-1 cells induced cleavage of pro-IL-1beta but not of pro-IL-33, and activated THP-1 cells released full-length pro-IL-33 into culture supernatants. Finally, addition of full-length pro-IL-33 induced T1/ST2-dependent IL-6 secretion in mast cells. However, we observed in situ processing of pro-IL-33 in mast cell cultures, and it remains to be determined whether full-length pro-IL-33 itself indeed represents the bioactive species. In conclusion, our data indicate that pro-IL-33 is not a direct substrate for caspase-1. In addition, our results clearly show that caspase-1 cleavage is not required for pro-IL-33 secretion and bioactivity, highlighting major differences between IL-1beta and IL-33.
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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.