guanosine-monophosphate and Non-alcoholic-Fatty-Liver-Disease

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.

Topics: Adenosine Monophosphate; Alarmins; Caspase 1; Guanosine Monophosphate; Humans; Inflammation; Inflammation Mediators; Interleukin-18; Interleukin-1beta; Liver Diseases, Alcoholic; NLR Family, Pyrin Domain-Containing 3 Protein; Non-alcoholic Fatty Liver Disease; Pathogen-Associated Molecular Pattern Molecules; Receptors, Pattern Recognition; Receptors, Purinergic P2X7; Signal Transduction; Toll-Like Receptor 4; Toll-Like Receptor 9; Tumor Necrosis Factor-alpha; Uric Acid

Today, nonalcoholic fatty liver disease remains the most dominant chronic liver disease. Cyclic guanosine monophosphate-adenosine monosphosphate synthase (cGAS) is a cytosolic DNA sensor that catalyzes the synthesis of cyclic guanosine monophosphate, activates stimulator of interferon genes (STING), and releases type-I interferon cytokines to trigger immune responses. Exogenous or endogenous DNA acts as a cGAS ligand to activate the cGAS-STING signaling pathway, which plays a role in hepatitis, nonalcoholic fatty liver disease, liver cancer and other diseases, and affects liver disease progression and metabolism through mechanisms such as autophagy. This article reviews the activation of cGAS-STING pathway and its molecular immunological role in nonalcoholic fatty liver disease progression.. 非酒精性脂肪性肝病仍是当今最主要的慢性肝病。细胞DNA传感器环磷酸鸟-腺苷合成酶（cGAS）通过催化合成环磷酸鸟苷，激活干扰素基因刺激因子（STING），释放以I型干扰素为代表的细胞因子引发免疫反应。外源或内源DNA为cGAS配体激活cGAS-STING信号通路，在肝炎、非酒精性脂肪肝疾病、肝癌等疾病中发挥作用，通过自噬和代谢等机制影响肝病进展。现综述非酒精性脂肪肝疾病进展中cGAS-STING通路激活及其分子免疫学作用。.

Topics: Guanosine Monophosphate; Humans; Interferon Type I; Membrane Proteins; Non-alcoholic Fatty Liver Disease; Nucleotidyltransferases; Signal Transduction