Metabolic inflammation as an instigator of fibrosis during non-alcoholic fatty liver disease

Table 1 Pathways and mediators of liver fibrosis during non-alcoholic fatty liver disease

Mediator	Expression in the liver	Function during NAFLD
TLR2	Kupffer cells, HSCs	Promotion of fibrogenesis via activation of MAPK and NF-κB signaling pathways
TLR4	Kupffer cells, HSCs	Induction of inflammation and fibrosis in a NF-κB-dependent way
ΤLR9	Kupffer cells, HSCs	HSC differentiation, secretion of IL-1β from Kupffer cells and MCP-1 from HSCs
NLRs	Innate immune cells hepatocytes, endothelial cells and HSCs	NAFLD and NASH development via inflammasome activation and release of IL-1β and IL-18
TNF-α	Kupffer cells, hepatocytes	Promotion of liver fibrosis by inducing the survival and proliferation of HSCs
IL-1α/ IL-1β	Kupffer cells	Stimulation of hepatocyte lipid accumulation and induction of fibrosis via MMP production and suppression of PPARα in HSCs
IL-6	Immune cells, Kupffer cells	Induction of hepatic lipogenesis in a Stat-3 dependent way
TGF-β	Kupffer cells, endothelial cells, HSCs	Induction of HSC activation and proliferation mainly via TGF-β-SMAD pathway
PDGF	Kupffer cells, activated HSCs, platelets	Induction of HSC migration, activation and proliferation via Ras-MAPK pathway

PPARα: Proliferator-activated receptor alpha activity; PDGF: Platelet-derived growth factor; NAFLD: Non-alcoholic fatty liver disease; HSCs: Hepatic stellate cells; NASH: Non-alcoholic steatohepatitis.