Table 1 The role of NLRP3 inflammasome in diseases

CAPS

Patients

Gain-of-function mutations of the NLRP3 gene result in the excessive activation of NLRP3 inflammasome that causes sustained and uncontrolled release of IL-1β.

[64]

CAPS

Patients and crossed Nlrp3^A350VNeoR^fl/+ mice with neutrophil-specific MRP8-Cre mice

NLRP3 inflammasome activation-induced cytokine IL-1β specifically enhances in neutrophils.

[68]

FMF

Patients

The monocytes from FMF patients secrete more NLRP3-dependent IL-1β.

[76]

AD

THY-Tau22 transgenic mice crossed with either Pycard-knockout mice (named Asc^−/−) or Cias1-knockout mice (named Nlrp3^−/−)

NLRP3 inflammasome activation induces tau hyperphosphorylation and aggregation.

[86]

PD

Patients

NLRP3 inflammasome activation aggravates the clinical features of PD through neuroinflammation.

[95]

PD

MPTP-induced PD mice model

NLRP3 inflammasome deficiency abolishes MPTP-induced microglial recruitment.

[99]

PD

Mice with microglial deletion of Atg5

NLRP3 inflammasome activation increases the expression of macrophage migration inhibitory factors and neuroinflammatory levels.

[100]

PD

Atg5^flox/flox mice intraperitoneally injected with MPTP to induce experimental PD model

NLRP3 inflammasome activation promotes neuroinflammation and dopaminergic neurodegeneration.

[101]

PD

MPTP-induced PD mice model

NLRP3 inflammasome activation promotes GSDMD cleavage and subsequent pyroptosis of microglia.

[102]

Spinal cord injury

Sprague–Dawley rat models with spinal cord injury

The ROS/TXNIP/NLRP3 signaling pathway aggravates neuroinflammation.

[107]

HD

R6/2 transgenic HD mice model

NF-κB/NLRP3 pathways contributes to neuroinflammation.

[108]

HD

R6/2 transgenic HD mice model

The NLRP3 inflammasome promotes pyroptosis of striatal neurons.

[109]

Atherogenesis

High-fat diet feeding

Hyperactivation of the NLRP3/caspase-1/IL-1β signaling pathway promote atherosclerosis.

[115]

Atherogenesis

Intraperitoneal injection of cholesterol crystals or high-cholesterol diet feeding

NLRP3 inflammasome activation and downstream cytokine release promote atherosclerosis.

[116]

Atherogenesis

High-fat diet feeding

Inhibition of thioredoxin-1/NLRP3 pathway has a protective effect on atherosclerosis.

[117]

Atherogenesis

Mice fed with high-fat diet or/and administrated with the water containing nicotine

ROS–NLRP3-mediated endothelial cell pyroptosis promotes atherosclerosis.

[118]

Dilated cardiomyopathy

Mice intraperitoneally injected with doxorubicin

NLRP3 inflammasome activation causes pyroptosis and myocardial dysfunction through caspase-1.

[121]

Heart failure

Mice undergo transverse aortic constriction surgery

Activation of NLRP3 inflammasome increases cardiac inflammation.

[122]

NASH

Mice fed with an atherogenic diet for 16 weeks, gavaged MCC950 until 24 weeks or mice fed a methionine/choline deficient diet, gavaged MCC950 for 6 weeks

Intracellular NLRP3 inflammasome activation enhances NASH inflammation.

[125]

NASH

Mice model of LPS/D-GalN-induced endotoxin acute hepatitis or fibrotic NASH resultant of long-term feeding with a high-fat, fructose, and cholesterol diet

Activation of NLRP3 inflammasome increases inflammation and promotes liver fibrosis development.

[132]

Liver cirrhosis

Patients

Activation of NLRP3 inflammasome increases plasma levels of IL-1β and IL-18 in patients with cirrhosis.

[134]

Liver cirrhosis

Mice intraperitoneally injected with CCL₄ to induce liver cirrhosis

After NLRP3 inflammasome activation, IL-1β is secreted extracellularly by the GSDMD pore to exert an inflammatory effect.

[135]

Liver fibrosis

Mice intraperitoneally injected with CCL4 or thioacetamide to induce liver cirrhosis

NLRP3 inflammasome activation increases liver inflammation by releasing proinflammatory factors.

[139, 140]

Liver fibrosis

A hepatocyte-specific NLRP3 heterozygous gain of function mutant mouse strain

Hepatocyte NLRP3 inflammasome activation leads to hepatocyte pyroptosis and secretion of inflammasome complexes into the extracellular space.

[141]

IBD

Oral DSS administration

NLRP3 inflammasome plays a protective role in intestinal mucosa by reducing the production of proinflammatory factors.

[144]

IBD

Oral DSS administration

Defective NLRP3 inflammasome activation leads to loss of epithelial integrity and systemic dispersion of commensal bacteria.

[145]

IBD

IL-10^−/− mice

NLRP3 inflammasome is activated in colonic mucosa and aggravates colorectal inflammation.

[146]

IBD

Mice are given DSS orally or given a rectal administration of 2,4,6-trinitrobenzene sulfonic acid

Inhibition of NLRP3 inflammasome activation can alleviate the symptoms of colitis in mice.

[149, 150]

UC

Oxazolone is delivered intrarectally to mice

The NLRP3 inflammasome-derived IL-1β and IL-18 play a protective role against UC.

[151]

IBD

Nlrp3^R258W mutant mice

NLRP3^R258W enhances IL-1β secretion, which boosts local antimicrobial peptides to facilitate microbiota remodeling.

[152]

RA

Patients and healthy individuals

NLRP3 gene loci are associated with susceptibility to RA.

[155]

RA

Collagen‐induced arthritis mice model

Activation of NLRP3 inflammasome increases joint inflammation and bone destruction.

[156]

RA

Patients

Activation of NLRP3 inflammasome produces IL-1β in rheumatoid arthritis.

[157]

RA

Patients

CaSR-mediated NLRP3 inflammasome activation contributes to inflammatory arthritis.

[158]

Chronic active gouty arthritis

Patients with rilonacept treatment

Blocking the downstream cytokines of NLRP3 inflammasome can effectively reduce inflammation and pain in patients.

[161]

Gout

Intra-articular injection MSU in the knee of rats

BHB inhibits NLRP3 inflammasome to reduce gout.

[163]