Toll-like receptor-mediated signaling cascade as a regulator of the inflammation network during alcoholic liver disease

Table 1 Experimental evidence of Toll-like receptor involvement in inflammation during alcoholic liver disease

Ref.	Experimental model	Upstream factor	Involved TLRs	Effects
Enomoto et al[39], 2000	Ethanol-fed rats	LPS	TLR4	Kupffer cell activation and consequent inflammation
Uesugi et al[40], 2001	TLR4 non-functional mice fed ethanol	LPS	TLR4	Decreased:
				Steatosis
				Inflammation
				Focal necrosis
Park et al[51], 2004	HEK293T cells	Nox4	TLR4	NF-κB activation
				LPS-mediated ROS generation
Gustot et al[48], 2006	Mice fed a modified Lieber-DeCarli diet			Increased:
		LTA, PGN	TLR2	Steatosis
		LPS	TLR4	Liver weight -aminotransferase levels
		flagellin	TLR5	Liver mRNA expression of different TLRs.
	Addition of multiple bacterial products			Increased:
		loxoribine	TLR7	TNF-α mRNA expression
		CpG	TLR9	Liver inflammatory infiltrate
Hritz et al[43], 2008	TLR4-(KO) mice feed Lieber-De-Carli diet		TLR4	Protection from:
				Alcohol-induced liver damage
				ROS production
				Inflammation
Bala et al[58], 2011	ALD mouse model	LPS	TLR4	MiRNA-155 increase and TNF-α levels in isolated KCs
Bala et al[59], 2012	ALD mouse model			Plasma increase of:
	administered with CpG + LPS	CpG	TLR9	miR-155, miR-122 and miR-146a
	TLR4-KO			Protection from:
		LPS	TLR4	Alcohol-induced liver disease
				Increase of both miR-155 and miR-122
Byun et al[61], 2013	Mice feed high-fat diet plus binge ethanol	poly I:C	TLR3	Protection from alcoholic liver damage
	TLR3 (KO) mice			Preservative action of poly I:C abrogated

LPS: Lipopolysaccharide; TLR: Toll-like receptor; LTA: Lipoteichoic acid; PGN: Peptidoglycan; TNF: Tumor necrosis factor; NADPH: Nicotinamide adenine dinucleotide phosphate; Nox4: NADPH oxidase 4; ROS: Reactive oxygen species; ALD: Alcoholic liver disease; KCs: Kupffer cells; poly I:C: Polyinosinic-polycytidylic acid.