Redox Regulation of NLRP3 Inflammasomes: ROS as Trigger or Effector?
Top Cited Papers
- 1 May 2015
- journal article
- review article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 22 (13), 1111-1129
- https://doi.org/10.1089/ars.2014.5994
Abstract
Significance: Inflammasomes are multiprotein complexes localized within the cytoplasm of the cell that are responsible for the maturation of proinflammatory cytokines such as interleukin-1β (IL-1β) and IL-18, and the activation of a highly inflammatory form of cell death, pyroptosis. In response to infection or cellular stress, inflammasomes are assembled, activated, and involved in host defense and pathophysiology of diseases. Clarification of the molecular mechanisms leading to the activation of this intracellular inflammatory machinery may provide new insights into the concept of inflammation as the root of and route to human diseases. Recent Advances: The activation of inflammasomes, specifically the most fully characterized inflammasome—the nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome, is now emerging as a critical molecular mechanism for many degenerative diseases. Several models have been developed to describe how NLRP3 inflammasomes are activated, including K+ efflux, lysosome function, endoplasmic reticulum (ER) stress, intracellular calcium, ubiquitination, microRNAs, and, in particular, reactive oxygen species (ROS). Critical Issues: ROS may serve as a “kindling” or triggering factor to activate NLRP3 inflammasomes as well as “bonfire” or “effector” molecules, resulting in pathological processes. Increasing evidence seeks to understand how this spatiotemporal action of ROS occurs during NLRP3 inflammasome activation, which will be a major focus of this review. Future Directions: It is imperative to know how this dual action of ROS works during NLRP3 inflammation activation on different stimuli and what relevance such spatiotemporal redox regulation of NLRP3 inflammasomes has in cell or organ functions and possible human diseases. Antioxid. Redox Signal. 22, 1111–1129.This publication has 153 references indexed in Scilit:
- Thioredoxin-Interacting Protein Mediates ER Stress-Induced β Cell Death through Initiation of the InflammasomeCell Metabolism, 2012
- Caspase-1: is IL-1 just the tip of the ICEberg?Cell Death & Disease, 2012
- Oxidized Mitochondrial DNA Activates the NLRP3 Inflammasome during ApoptosisImmunity, 2012
- ER stress activates the NLRP3 inflammasome via an UPR-independent pathwayCell Death & Disease, 2011
- The Inflammasome-Mediated Caspase-1 Activation Controls Adipocyte Differentiation and Insulin SensitivityCell Metabolism, 2010
- Protection of podocytes from hyperhomocysteinemia-induced injury by deletion of the gp91phox geneFree Radical Biology & Medicine, 2010
- ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell functionToxicology and Applied Pharmacology, 2010
- Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic DiseaseCell, 2010
- Sterile inflammatory responses mediated by the NLRP3 inflammasomeEuropean Journal of Immunology, 2010
- The Intracellular Sensor NLRP3 Mediates Key Innate and Healing Responses to Influenza A Virus via the Regulation of Caspase-1Immunity, 2009