Review
Nrf2 signaling pathway: Pivotal roles in inflammation

https://doi.org/10.1016/j.bbadis.2016.11.005Get rights and content
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Highlights

  • Nrf2 involves in inflammatory diseases.

  • Crosstalk between Nrf2 and NF-ĸB pathways.

  • Nrf2 regulates NLRP3 inflammasome activity.

  • Nrf2 pathway could be therapeutically exploited.

Abstract

Inflammation is the most common feature of many chronic diseases and complications, while playing critical roles in carcinogenesis. Several studies have demonstrated that Nrf2 contributes to the anti-inflammatory process by orchestrating the recruitment of inflammatory cells and regulating gene expression through the antioxidant response element (ARE). The Keap1 (Kelch-like ECH-associated protein)/Nrf2 (NF-E2 p45-related factor 2)/ARE signaling pathway mainly regulates anti-inflammatory gene expression and inhibits the progression of inflammation. Therefore, the identification of new Nrf2-dependent anti-inflammatory phytochemicals has become a key point in drug discovery. In this review, we discuss the members of the Keap1/Nrf2/ARE signal pathway and its downstream genes, the effects of this pathway on animal models of inflammatory diseases, and crosstalk with the NF-κB pathway. In addition we also discuss about the regulation of NLRP3 inflammasome by Nrf2. Besides this, we summarize the current scenario of the development of anti-inflammatory phytochemicals and others that mediate the Nrf2/ARE signaling pathway.

Abbreviations

ARE
antioxidant response element
CBP
cAMP-response-element-binding protein binding protein
COX-2
cyclooxygenase 2
Gclc
glutamate cysteine ligase catalytic subunit
Gclm
glutamate cysteine ligase regulatory subunit
GSH
glutathione
HO-1
heme oxygenase-1
IKKβ
inhibitor of nuclear factor kappa-B kinase
ICAM-1
intercellular adhesion molecule1
IL-17
interleukin 17
IL-6
interleukin 6
JAK
janus kinase
KEAP1
Kelch-like ECH associated protein
LDL
low-density lipoprotein
LPS
lipopolysaccharide
MAPK
mitogen-activated protein kinase
MCP1
monocyte chemoattractant protein-1
MIP2
macrophage inflammatory protein 2
MMP-7
matrix metalloproteinase 7
MMP-9
matrix metalloproteinase 9
NAD(P)H
nicotinamide adenine dinucleotide phosphate
NF-κB
nuclear factor – κB
NRF2
NF-E2 p45-related factor 2
PrxI
peroxiredoxin I
ROS
reactive oxygen species
RXRα
retinoid X receptor alpha
STAT
signal transducers and activators of transcription
TREM1
triggering receptor expressed on myeloid cells 1
Th1
T helper cell 1
Th17
T helper cell 17
TNF-α
tumor necrosis factor α
VCAM-1
vascular cell adhesion molecule 1

Keywords

Nrf2
Keap1
ARE
Inflammation
Oxidative stress
Phytochemical

Cited by (0)

1

Equal contribution.