Table 1.

The role of NLRP3 inflammasome in diseases

Disease	Model/patients	Mechanism	References
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 Nlrp3A350VNeoRfl/+ 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	Atg5flox/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	Nlrp3R258W mutant mice	NLRP3R258W 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]