Research progress on the inflammatory mechanisms of cholestatic liver injury

doi:10.16352/j.issn.1001-6325.2022.05.002

Abstract

Abstract: Cholestatic liver injury (CLI) is a liver disease with high mordity. Accumulation of bile acids in the liver is thought to be a major driver of liver injury during cholestasis. The disease can develop into be liver fibrosis, cirrhosis, liver failure and liver cancer. This review focuses on the molecular mechanism of CLI in the perspective of inflammatory response. The roles of neutrophils, Kupffer cells, bile duct cells, and the signaling pathways involved in CLI are reviewed to provide clues for research of new therapeutic targets and treatment strategies.

Key words: cholestatasis, liver injury, inflammation, neutrophils, c-Jun N-terminal kinase

CLC Number:

R575

KANG Jin-yu, LUO Jia, GAO Ze-tian, ZHENG Wen-tao, LIU Ai-ming, SONG Yu-fei. Research progress on the inflammatory mechanisms of cholestatic liver injury[J]. Basic & Clinical Medicine, 2022, 42(5): 809-813.

References

[1] Apajalahti J, Vienola K, Raatikainen K, et al. Distribution, metabolism, and recovery of resin acids in the intestine and tissues of broiler chickens in a feeding trial with tall oil fatty acid-supplemented diets[J]. Front Vet Sci, 2020, 7: 437. doi: 10.3389/fvets.2020.00437.
[2]Blokker BA, Maijo M, Echeandia M, et al. Fine-tuning of sirtuin 1 expression is essential to protect the liver from cholestatic liver disease[J]. Hepatology, 2019, 69: 699-716.
[3]Takada S, Matsubara T, Fujii H, et al. Stress can attenuate hepatic lipid accumulation via elevation of hepatic beta-muricholic acid levels in mice with nonalcoholic steatohepatitis[J]. Lab Invest, 2021, 101: 193-203.
[4]Schölmerich J, Becher MS, Schmidt K, et al. Influence of Hydroxylation and conjugation of bile salts on their membrane‐damaging properties‐studies on isolated hepatocytes and lipid membrane vesicles[J]. Hepatology, 1984, 4: 661-666.
[5]Woolbright BL, Dorko K, Antoine DJ, et al. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis[J]. Toxicol Appl Pharmacol, 2015, 283: 168-177.
[6]Cai S, Boyer JL. The role of inflammation in the mechanisms of bile acid-Induced liver damage[J]. Dig Dis, 2017, 35: 232-234.
[7]Woolbright BL, Antoine DJ, Jenkins RE, et al. Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice[J]. Toxicol Appl Pharmacol, 2013, 273: 524-531.
[8]Yang M, Ramachandran A, Yan H, et al. Osteopontin is an initial mediator of inflammation and liver injury during obstructive cholestasis after bile duct ligation in mice[J]. Toxicol Lett, 2014, 224: 186-195.
[9]Cai S, Ouyang X, Chen Y, et al. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response[J]. JCI Insight, 2017, 2: e90780. doi: 10.1172/jci.insight.90780.
[10] Rayapuram N, Bigeard J, Alhoraibi H, et al. Quantitative phosphoproteomic analysis reveals shared and specific targets of arabidopsis mitogen-activated protein kinases (MAPKs) MPK3, MPK4, and MPK6[J]. Mol Cell Proteomics,2018, 17: 61-80.
[11] Allen K, Kim ND, Moon J, et al. Upregulation of early growth response factor-1 by bile acids requires mitogenac-tivated protein kinase signaling[J]. Toxicol Appl Pharmacol, 2010, 243: 63-67.
[12] Mateu A, De Dios I, Manso MA, et al. Oxidized phospholipids exert a dual effect on bile acid-induced CCL2 expression in pancreatic acini[J]. Pancreatology, 2017, 17: 372-380.
[13] Gehrke N, Nagel M, Straub BK, et al. Loss of cellular FLICE-inhibitory protein promotes acute cholestatic liver injury and inflammation from bile duct ligation[J]. Am J Physiol Gastrointest Liver Physiol, 2018, 314: G319-G333.
[14] Dai M, Yang J, Xie M, et al. Inhibition of JNK signalling mediates PPARα-dependent protection against intrahepatic cholestasis by fenofibrate[J]. British J Pharmacol, 2017, 174: 3000-3017.
[15] Dai M, Yang J, Luo Y, et al. Therapeutic action against chronic cholestatic liver injury by low-dose fenofibrate involves anti-chemotaxis via JNK-AP1-CCL2/CXCL2 signaling[J]. Pharmacol Rep,2020, 72: 935-944.
[16] Xu G, Dai M, Zheng X, et al. Cholestatic models induced by lithocholic acid and α-naphthylisothiocyanate: Different etiological mechanisms for liver injury but shared JNK/STAT3 signaling[J]. Mole Med Reports, 2020, 22: 1583-1593.
[17] Sorrentino G, Perino A, Yildiz E, et al. Bile acids signal via TGR5 to activate intestinal stem cells and epithelial regeneration[J]. Gastroenterology, 2020, 159: 956-968.
[18] Lou G, Ma X, Fu X, et al. GPBAR1/TGR5 mediates bile acid-induced cytokine expression in murine Kupffer cells[J]. PLoS One, 2014, 9: e93567. doi: 10.1371/journal.pone.0093567.
[19] Li T, Holmstrom SR, Kir S, et al. The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling[J]. Mol Endocrinol, 2011, 25: 1066-1071.
[20] Perino A, Pols TWH, Nomura M, et al. TGR5 reduces macrophage migration through mTOR-induced C/EBPβ differential translation[J]. J Clin Investigation,2014, 124: 5424-5436.
[21] Sasaki M, Ikeda H, Yamaguchi J, et al. Bile ductular cells undergoing cellular senescence increase in chronic liver diseases along with fibrous progression[J]. Am J Clin Pathol, 2010, 133: 212-223.
[22] Ferreira-Gonzalez S, Lu W, Raven A, et al. Paracrine cellular senescence exacerbates biliary injury and impairs regeneration[J]. Nat Commun, 2018, 9: 1020. doi: 10.1038/s41467-018-03299-5.
[23] Maeso-Diaz R, Ortega-Ribera M, Fernandez-Iglesias A, et al. Effects of aging on liver microcirculatory function and sinusoidal phenotype[J]. Aging Cell, 2018, 17: e12829. doi: 10.1111/acel.12829.
[24] 肖黎明,杨莹,崔涵,等. 异柠檬酸脱氢酶1对肝内胆管细胞癌中炎性反应的影响[J]. 基础医学与临床, 2019, 39: 1556-1560.