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

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

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)
Venue
Annual Review of Immunology
Published
2015-03-21
Volume
33
Issue
1
Pages
49-77
ISSN
  • 0732-0582 (ISSN-L)
  • 1545-3278
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
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
  • Health Sciences › Medicine › Oncology › 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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