Abstract
Hepatic inflammation is prevalent in several metabolic liver diseases. Recent scientific advances about the pathogenesis of metabolic liver diseases showed an emerging role of several damage-associated molecular patterns (DAMPs), including DNA, high-mobility group box 1 (HMGB1), ATP and uric acid. For these DAMPs to induce inflammation, they should stimulate pattern recognition receptors (PRRs), which are located in the hepatic immune cells like resident Kupffer cells, infiltrated neutrophils, monocytes or dendritic cells. As a consequence, proinflammatory cytokines like interleukins (ILs)-1β and 18 alongside tumor necrosis factor (TNF)-α are overproduced and released, leading to pronounced hepatic inflammation and cellular death. This review highlights the contribution of these DAMPs and PRRs in the settings of alcoholic and nonalcoholic steatohepatitis. The review also summarizes the therapeutic usefulness of targeting NLR family pyrin domain containing 3 (NLRP3)-inflammasome, Toll-like receptors (TLRs) 4 and 9, IL-1 receptor (IL-1R), caspase 1, uric acid and GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) in these hepatic inflammatory disorders.
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•The outcomes for liver steatosis are similar, but the pathogenesis is different.•Inflammation danger signals like PAMPs and DAMPs were implicated in steatohepatitis.•Understanding the diversity of danger signals and their PRRs is important in management.•Therapeutic strategies are directed toward interference with TLRs 4 and 9 are highlighted.•Other therapeutic strategies like targeting NLRP-3 and P2X7 are also considered.