Table 1.

The role of NOD1, NOD2 and NLRP3 in liver disease, with focus on the experimental model and regulation mechanism

NLR	Liver disease	Experimental models	Role in liver disease	Reference
NOD1	liver inflammation and infection	C57BL/6 mice	Stimulate hepatocytes with NOD1 ligand (C12-iEDAP) inducing NF-κB activation, activate MAP kinases, express chemokines CCL5 (RANTES) and CXCL1 (KC)	[30]
	LPS-induced liver injury	pigs	NOD1 and its adaptor molecule (RIPK2) were reduced, and the level of liver TNF-α was decreased simultaneously in the pigs fed a fish oil diet after LPS challenge.	[118]
	polymorphonuclear neutrophils (PMN)-induced liver injury.	mice	invalidation of NOD1 protects against PMN induced liver injury in the I/R model	[31]
NOD2	LPS-induced liver injury	pigs	NOD2 and its adaptor molecule (RIPK2) were reduced in the pigs fed a fish oil diet	[118]
	concanavalin A-induced liver injury	C57BL/6 mice	a regulatory mechanism affecting immune cells infiltrating the liver and hepatocytes	[32]
NLRP3	Liver ischemia-reperfusion (I/R) injury	Male C57BL/6J mice/liver nonparenchymal cells (NPCs)	Silencing NLRP3 ameliorated I/R-induced hepatocellular injury and reduced IL-1β, IL-18, HMGB1, IL-6, and TNFα release via inhibition of caspase-1 and NF-κB activity	[83]
	acetaminophen-induced liver injury	mice	NLRP3 inflammasome pathway play the important role in generating mature IL-1β and IL-18	[15]
	Endotoxin-induced Liver Injury	mice	TLR4/NLRP3-mediated caspase-1 activation process	[33]
	alcoholic hepatitis (AH) liver disease	liver biopsies	NRLP3 was not upregulate but rather NAIP was upregulated	[26]
	Non-alcoholic fatty liver disease (NAFLD)	mice	NlRP3-/- mice developed exacerbated NASH compared to wt mice	[14]
	Chronic hepatitis C virus (HCV) infection	THP-1 cells	NLRP3 inflammasome stimulates IL-1β production to drive proinflammatory cytokine, chemokine, and immune-regulatory gene expression networks linked with HCV disease severity	[34]
	liver fibrosis	LX-2 cells, Primary HSCs, Mice	Mice lacking the inflammasome-sensing and adaptor molecules, NLRP3 and apoptosis-associated speck-like protein containing CARD, reduced CCl4 and TAA-induced liver fibrosis.	[29]
	LPS-induced liver damage	mice	activate the NLRP3 inflammasome and caspase-1, secrete IL-1β and IL-18	[33]