Generation of biologically active interleukin-1 beta by proteolytic cleavage of the inactive precursor.

Black, Roy A.; Kronheim, С.; Cantrell, Michael A.; Deeley, M C; March, Carl J.; Prickett, K S; Wignall, J; Conlon, Paul; Cosman, David; Hopp, Thomas P.

doi:10.1016/s0021-9258(19)76559-4

Cited by 333 publications

(40 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pro-IL-1β is not considered biologically active. However, proteases derived from neutrophils and pathogens such as S. aureus are able to process pro-IL-1β into active molecules ( 46 , 47 ). Specifically, in models of acute arthritis, proteinase 3 from neutrophils can cleave pro-IL-1β ( 48 ) and MAC deposition is known to be elevated in the context of arthritis ( 17 , 18 ).…”

Section: Discussionmentioning

confidence: 99%

Internalization of the Membrane Attack Complex Triggers NLRP3 Inflammasome Activation and IL-1β Secretion in Human Macrophages

et al. 2021

View full text Add to dashboard Cite

Interleukin 1β (IL-1β) plays a major role in inflammation and is secreted by immune cells, such as macrophages, upon recognition of danger signals. Its secretion is regulated by the inflammasome, the assembly of which results in caspase 1 activation leading to gasdermin D (GSDMD) pore formation and IL-1β release. During inflammation, danger signals also activate the complement cascade, resulting in the formation of the membrane attack complex (MAC). Here, we report that stimulation of LPS-primed human macrophages with sub-lytic levels of MAC results in activation of the NOD-like receptor 3 (NLRP3) inflammasome and GSDMD-mediated IL-1β release. The MAC is first internalized into endosomes and then colocalizes with inflammasome components; adapter protein apoptosis associated speck-like protein containing a CARD (ASC) and NLRP3. Pharmacological inhibitors established that MAC-triggered activation of the NLRP3 inflammasome was dependent on MAC endocytosis. Internalization of the MAC also caused dispersion of the trans-Golgi network. Thus, these data uncover a role for the MAC in activating the inflammasome and triggering IL-1β release in human macrophages.

show abstract

Section: Discussionmentioning

confidence: 99%

Internalization of the Membrane Attack Complex Triggers NLRP3 Inflammasome Activation and IL-1β Secretion in Human Macrophages

et al. 2021

View full text Add to dashboard Cite

show abstract

“…4 IL-1β is synthesized as a premature cytokine termed pro-IL-1β. [13][14][15][16] The synthesis of the functional mature, active IL-1β is highly regulated and can be subdivided into two stages, namely priming (signal one) and activation (signal two) (Figure 1). 17 During priming, a cell is stimulated through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs) by pathogen-associated molecular patterns (PAMPs) and damageassociated molecular patterns (DAMPs).…”

Section: Structure and Production Of Il-1βmentioning

confidence: 99%

The role of interleukin‐1β in the immune response to contact allergens

et al. 2021

View full text Add to dashboard Cite

Interleukin-1β (IL-1β) is an important pro-inflammatory cytokine that has an effect on almost every cell lineage in the body. By blocking IL-1β and investigating the IL-1β signaling pathway, several studies have demonstrated a central role of IL-1β in the response to contact allergens. This review summarizes the current literature regarding the basic immunological mechanisms mediated by IL-1β in the different phases of allergic contact dermatitis (ACD) and highlights potential IL-1β-targeted treatment options, which in the future may be relevant in the treatment of patients with ACD.This review is based primarily on studies using various mouse models and human in vitro studies, since clinical studies on the effect of IL-1β in ACD are lacking.

show abstract

“…Although only 23% homologous at the amino acid level, the tertiary structures of IL-1a and IL-1b are quite similar, consisting of 12b-pleated sheets and a distinctive barrel-like form (Dinarello, 1996). The 31 kDa IL-1a is biologically active (Mosley et al, 1987), but 31 KD IL-1b must be cleaved by interleukin-1b converting enzyme (ICE; recently renamed as caspase-1) to generate an active molecule (Black et al, 1988); this occurs concurrently with release from the cell through an incompletely understood pathway. IL-1a can be cleaved by calpain to a 17 kDa form (Kobayashi et al, 1990).…”

Section: Interleukin-1mentioning

confidence: 99%

Interleukin-1 and Cutaneous Inflammation: A Crucial Link Between Innate and Acquired Immunity

Murphy¹,

Robert²,

Kupper³

2000

Journal of Investigative Dermatology

188

130

View full text Add to dashboard Cite

As our primary interface with the environment, the skin is constantly subjected to injury and invasion by pathogens. The fundamental force driving the evolution of the immune system has been the need to protect the host against overwhelming infection. The ability of T and B cells to recombine antigen receptor genes during development provides an efficient, flexible, and powerful immune system with nearly unlimited specificity for antigen. The capacity to expand subsets of antigen-specific lymphocytes that become activated by environmental antigens (memory response) is termed "acquired" immunity. Immunologic memory, although a fundamental aspect of mammalian biology, is a relatively recent evolutionary event that permits organisms to live for years to decades. "Innate" immunity, mediated by genes that remain in germ line conformation and encode for proteins that recognize conserved structural patterns on microorganisms, is a much more ancient system of host defense. Defensins and other antimicrobial peptides, complement and opsonins, and endocytic receptors are all considered components of the innate immune system. None of these, however, are signal-transducing receptors. Most recently, a large family of cell surface receptors that mediate signaling through the NF-kappaB transcription factor has been identified. This family of proteins shares striking homology with plant and Drosophila genes that mediate innate immunity. In mammals, this family includes the type I interleukin-1 receptor, the interleukin-18 receptor, and a growing family of Toll-like receptors, two of which were recently identified as signal-transducing receptors for bacterial endotoxin. In this review, we discuss how interleukin-1 links the innate and acquired immune systems to provide synergistic host defense activities in skin.

show abstract

Generation of biologically active interleukin-1 beta by proteolytic cleavage of the inactive precursor.

Cited by 333 publications

References 29 publications

Internalization of the Membrane Attack Complex Triggers NLRP3 Inflammasome Activation and IL-1β Secretion in Human Macrophages

Internalization of the Membrane Attack Complex Triggers NLRP3 Inflammasome Activation and IL-1β Secretion in Human Macrophages

The role of interleukin‐1β in the immune response to contact allergens

Interleukin-1 and Cutaneous Inflammation: A Crucial Link Between Innate and Acquired Immunity

Contact Info

Product

Resources

About