Table 3.

Modulation of neutrophil-related factors that affect the degree of experimental NASH.

	Modulation method	NASH induction model	Effect on NASH pathology	Reference
MPO	Deletion of the gene encoding MPO	HFHCD feeding in mice	↓ liver injury and liver fibrosis	(91)
	Pharmacological inhibition of MPO by AZM198 treatment	HFHCD feeding in mice	↓ liver injury and liver fibrosis	(91)
NE	Deletion of the gene encoding NE	HFD feeding in mice	↓ hepatic lipid content and inflammation	(141)
	Deletion of the gene encoding NE	Western diet feeding in mice	↓ steatosis and liver inflammation	(134)
	NE inhibition by sivelestat	HFHCD feeding in Apoe−/− mice	↓ steatosis, liver injury, inflammation, and NASH score	(142)
LCN2	Deletion of the gene encoding LCN2	HFHCD feeding in Apoe−/− mice	↓ liver injury, inflammation, and NASH score	(135)
	Treatment of recombinant LCN2	HFHCD feeding in Apoe−/− mice	↑ liver injury, inflammation, and NASH score	(135)
NET formation	DNase treatment	STAM mice	↓ hepatic macrophage infiltration, liver inflammation, and NASH activity score	(92)
	Deletion of the gene encoding PAD4	STAM mice	↓ hepatic macrophage infiltration, liver inflammation, and NASH activity score	(92)
	DNase treatment	MCDHFD feeding in mice	↓ liver injury, inflammation, and fibrosis	(140)
CXCL1, IL-8	Overexpression of CXCL1 and/or IL-8	HFD feeding in mice	↑ liver injury, inflammation, and fibrosis	(16, 89)

APOE, apolipoprotein E; CXCL1, C-X-C motif chemokine ligand 1; HFD, high-fat diet; HFHCD, high-fat, high-cholesterol diet; IL-8, interleukin-8; LCN2, lipocalin 2; MCDHFD, methionine-choline-deficient high-fat diet; MPO, myeloperoxidase; NASH; nonalcoholic steatohepatitis; NE, neutrophil elastase; NET, neutrophil extracellular trap; PAD4, peptidyl arginine deiminase-4; STAM, Stelic animal model of NASH.