Cited by 330Inflammasome and immune disordersImmune Response and InflammationCytokine Signaling Pathways and Interactions

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Inflammasome-Independent Regulation of IL-1-Family Cytokines

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Netea, Mihai G., van de Veerdonk, Frank L., van der Meer, Jos W.M., Dinarello, Charles A., Joosten, Leo A.B.·2015·Annual Review of Immunology

DOI 10.1146/annurev-immunol-032414-112306

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Abstract

Induction, production, and release of proinflammatory cytokines are essential steps to establish an effective host defense. Cytokines of the interleukin-1 (IL-1) family induce inflammation and regulate T lymphocyte responses while also displaying homeostatic and metabolic activities. With the exception of the IL-1 receptor antagonist, all IL-1 family cytokines lack a signal peptide and require proteolytic processing into an active molecule. One such unique protease is caspase-1, which is activated by protein platforms called the inflammasomes. However, increasing evidence suggests that inflammasomes and caspase-1 are not the only mechanism for processing IL-1 cytokines. IL-1 cytokines are often released as precursors and require extracellular processing for activity. Here we review the inflammasome-independent enzymatic processes that are able to activate IL-1 cytokines, paying special attention to neutrophil-derived serine proteases, which subsequently induce inflammation and modulate host defense. The inflammasome-independent processing of IL-1 cytokines has important consequences for understanding inflammatory diseases, and it impacts the design of IL-1-based modulatory therapies.

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Authors: Netea, M. G., van de Veerdonk, F. L., van der Meer, J. W. M., Dinarello, C. A., & Joosten, L. A. B.
Affiliations: Radboud University Medical Center (NL)
Department of Internal Medicine,
University of Colorado Anschutz (US)
ORCID: Netea, Mihai G.
Dinarello, Charles A.
Joosten, Leo A.B.
Venue: Annual Review of Immunology
Publisher: Annual Reviews
Published: 2015-03-21
Volume: 33
Issue: 1
Pages: 49-77
ISSN: 0732-0582 (ISSN-L)
1545-3278
DOI: 10.1146/annurev-immunol-032414-112306
OpenAlex: W2156301166
Cited by: 326
References: 228
Citations by year: 2026: 8 · 2025: 6 · 2024: 26 · 2023: 15 · 2022: 24 · 2021: 27 · 2020: 30 · 2019: 33 · 2018: 46 · 2017: 46 · 2016: 41 · 2015: 24
FWCI: 3.49
Type: journal article
Language: en
Open access: green
hdl.handle.net
Locations: Annual Review of Immunology (publishedVersion)
PubMed (publishedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Funders: National Institutes of Health (CA-04-6934, 15614, AI‐15614)
National Cancer Institute (CA 046934, P30CA046934)
National Institute of Allergy and Infectious Diseases (AI‑15614)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR‑45584, R01AR045584)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: caspase-1, neutrophil serine proteases, inflammatory cytokines, cytokine activation, host defense, inflammatory diseases
MeSH terms: Animals, Disease Susceptibility, Humans, Inflammation, Interleukin-1, Cytokines, Inflammation Mediators, Inflammasomes

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Inflammasome-Independent Regulation of IL-1-Family Cytokines

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