Redox Regulation of NLRP3 Inflammasomes: ROS as Trigger or Effector?

Justine M. Abais, Min Xia, Yang Zhang, Krishna M. Boini, Pin Lan Li

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
Pages (from-to)1111-1129
Number of pages19
JournalAntioxidants and Redox Signaling
Volume22
Issue number13
DOIs
StatePublished - May 1 2015

Fingerprint

Inflammasomes
Oxidation-Reduction
Reactive Oxygen Species
Chemical activation
Inflammation
Pyrin Domain
NLR Proteins
Multiprotein Complexes
Oligomerization
Interleukin-18
Endoplasmic Reticulum Stress
Ubiquitination
Cell death
Pathologic Processes
Lysosomes
MicroRNAs
Interleukin-1
Machinery
Cytoplasm
Cell Death

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Redox Regulation of NLRP3 Inflammasomes : ROS as Trigger or Effector? / Abais, Justine M.; Xia, Min; Zhang, Yang; Boini, Krishna M.; Li, Pin Lan.

In: Antioxidants and Redox Signaling, Vol. 22, No. 13, 01.05.2015, p. 1111-1129.

Research output: Contribution to journalReview article

Abais, JM, Xia, M, Zhang, Y, Boini, KM & Li, PL 2015, 'Redox Regulation of NLRP3 Inflammasomes: ROS as Trigger or Effector?', Antioxidants and Redox Signaling, vol. 22, no. 13, pp. 1111-1129. https://doi.org/10.1089/ars.2014.5994
Abais, Justine M. ; Xia, Min ; Zhang, Yang ; Boini, Krishna M. ; Li, Pin Lan. / Redox Regulation of NLRP3 Inflammasomes : ROS as Trigger or Effector?. In: Antioxidants and Redox Signaling. 2015 ; Vol. 22, No. 13. pp. 1111-1129.
@article{ab47155739dd42d58d29bc7c699c05f0,
title = "Redox Regulation of NLRP3 Inflammasomes: ROS as Trigger or Effector?",
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.",
author = "Abais, {Justine M.} and Min Xia and Yang Zhang and Boini, {Krishna M.} and Li, {Pin Lan}",
year = "2015",
month = "5",
day = "1",
doi = "10.1089/ars.2014.5994",
language = "English (US)",
volume = "22",
pages = "1111--1129",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "13",

}

TY - JOUR

T1 - Redox Regulation of NLRP3 Inflammasomes

T2 - ROS as Trigger or Effector?

AU - Abais, Justine M.

AU - Xia, Min

AU - Zhang, Yang

AU - Boini, Krishna M.

AU - Li, Pin Lan

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84924034834&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924034834&partnerID=8YFLogxK

U2 - 10.1089/ars.2014.5994

DO - 10.1089/ars.2014.5994

M3 - Review article

C2 - 25330206

AN - SCOPUS:84924034834

VL - 22

SP - 1111

EP - 1129

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 13

ER -