A clinical perspective of IL-1β as the gatekeeper of inflammation
TLDR
Evidence for the involvement of IL‐1β and the clinical results of reducing IL‐ 1β activity in this broad spectrum of inflammatory diseases are the focus of this review.Abstract:
An expanding spectrum of acute and chronic non-infectious inflammatory diseases is uniquely responsive to IL-1β neutralization. IL-1β-mediated diseases are often called "auto-inflammatory" and the dominant finding is the release of the active form of IL-1β driven by endogenous molecules acting on the monocyte/macrophage. IL-1β activity is tightly controlled and requires the conversion of the primary transcript, the inactive IL-1β precursor, to the active cytokine by limited proteolysis. Limited proteolysis can take place extracellularly by serine proteases, released in particular by infiltrating neutrophils or intracellularly by the cysteine protease caspase-1. Therefore, blocking IL-1β resolves inflammation regardless of how the cytokine is released from the cell or how the precursor is cleaved. Endogenous stimulants such as oxidized fatty acids and lipoproteins, high glucose concentrations, uric acid crystals, activated complement, contents of necrotic cells, and cytokines, particularly IL-1 itself, induce the synthesis of the inactive IL-1β precursor, which awaits processing to the active form. Although bursts of IL-1β precipitate acute attacks of systemic or local inflammation, IL-1β also contributes to several chronic diseases. For example, ischemic injury, such as myocardial infarction or stroke, causes acute and extensive damage, and slowly progressive inflammatory processes take place in atherosclerosis, type 2 diabetes, osteoarthritis and smoldering myeloma. Evidence for the involvement of IL-1β and the clinical results of reducing IL-1β activity in this broad spectrum of inflammatory diseases are the focus of this review.read more
Citations
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Journal ArticleDOI
Human Monocytes Engage an Alternative Inflammasome Pathway
Moritz M. Gaidt,Thomas S. Ebert,Dhruv Chauhan,Tobias Schmidt,Jonathan L. Schmid-Burgk,Francesca Rapino,Avril A. B. Robertson,Mark E. Cooper,Thomas Graf,Veit Hornung,Veit Hornung +10 more
TL;DR: A pivotal role is proposed for this signaling cascade in TLR4-driven, IL-1β-mediated immune responses and immunopathology in humans and it is reported that this constituted a species-specific response that is not observed in the murine system.
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NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases
Amna Abderrazak,Tatiana Syrovets,Dominique Couchie,Khadija El Hadri,Bertrand Friguet,Thomas Simmet,Mustapha Rouis,Mustapha Rouis,Mustapha Rouis +8 more
TL;DR: This review has updated knowledge on NLRP3 inflammasome assembly and activation and on the pyrin domain inNLRP3 that could represent a drug target to treat sterile inflammatory diseases, and reported mutations in NL RP3 that were found to be associated with certain diseases.
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Neutrophil cell surface receptors and their intracellular signal transduction pathways
TL;DR: The various cell surface receptors trigger very diverse signal transduction pathways including activation of heterotrimeric and monomeric G-proteins, receptor-induced and store-operated Ca2 + signals, protein and lipid kinases, adapter proteins and cytoskeletal rearrangement.
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Resolving postoperative neuroinflammation and cognitive decline
Niccolò Terrando,Lars Eriksson,Lars Eriksson,Jae K. Ryu,Ting Yang,Claudia Monaco,Marc Feldmann,Malin Jonsson Fagerlund,Israel F. Charo,Katerina Akassoglou,Mervyn Maze +10 more
TL;DR: This work sought to understand the mechanisms whereby the brain is targeted by the inflammatory response and how this can be resolved.
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NLRC4-driven production of IL-1β discriminates between pathogenic and commensal bacteria and promotes host intestinal defense.
Luigi Franchi,Nobuhiko Kamada,Yuumi Nakamura,Aaron Burberry,Peter Kuffa,Shiho Suzuki,Michael H. Shaw,Yun Gi Kim,Guillermo Gabriel Nuñez +8 more
TL;DR: NLRC4-dependent production of IL-1β by intestinal phagocytes represents a specific response that discriminates pathogenic bacteria from commensal bacteria and contributes to host defense in the intestine.
References
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NALP3 Forms an IL-1β-Processing Inflammasome with Increased Activity in Muckle-Wells Autoinflammatory Disorder
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