Article ; Online: Uncoupled pyroptosis and IL-1β secretion downstream of inflammasome signaling.
2023 Volume 14, Page(s) 1128358
Abstract: Inflammasomes are supramolecular platforms that organize in response to various damage-associated molecular patterns and pathogen-associated molecular patterns. Upon activation, inflammasome sensors (with or without the help of ASC) activate caspase-1 ... ...
Abstract | Inflammasomes are supramolecular platforms that organize in response to various damage-associated molecular patterns and pathogen-associated molecular patterns. Upon activation, inflammasome sensors (with or without the help of ASC) activate caspase-1 and other inflammatory caspases that cleave gasdermin D and pro-IL-1β/pro-IL-18, leading to pyroptosis and mature cytokine secretion. Pyroptosis enables intracellular pathogen niche disruption and intracellular content release at the cost of cell death, inducing pro-inflammatory responses in the neighboring cells. IL-1β is a potent pro-inflammatory regulator for neutrophil recruitment, macrophage activation, and T-cell expansion. Thus, pyroptosis and cytokine secretion are the two main mechanisms that occur downstream of inflammasome signaling; they maintain homeostasis, drive the innate immune response, and shape adaptive immunity. This review aims to discuss the possible mechanisms, timing, consequences, and significance of the two uncoupling preferences downstream of inflammasome signaling. While pyroptosis and cytokine secretion may be usually coupled, pyroptosis-predominant and cytokine-predominant uncoupling are also observed in a stimulus-, cell type-, or context-dependent manner, contributing to the pathogenesis and development of numerous pathological conditions such as cryopyrin-associated periodic syndromes, LPS-induced sepsis, and |
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MeSH term(s) | Inflammasomes/metabolism ; Pyroptosis/physiology ; Intracellular Signaling Peptides and Proteins/metabolism ; Phosphate-Binding Proteins/metabolism ; Caspases/metabolism ; Caspase 1/metabolism |
Chemical Substances | Inflammasomes ; Intracellular Signaling Peptides and Proteins ; Phosphate-Binding Proteins ; Caspases (EC 3.4.22.-) ; Caspase 1 (EC 3.4.22.36) |
Language | English |
Publishing date | 2023-04-06 |
Publishing country | Switzerland |
Document type | Journal Article ; Review ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2606827-8 |
ISSN | 1664-3224 ; 1664-3224 |
ISSN (online) | 1664-3224 |
ISSN | 1664-3224 |
DOI | 10.3389/fimmu.2023.1128358 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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