Reactive oxygen and mechanisms of inflammatory liver injury: Present concepts

Journal of Gastroenterology and Hepatology (Australia) - Tập 26 Số s1 - Trang 173-179 - 2011
Hartmut Jaeschke1
1Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, 66160, USA. hjaeschke@kumc.edu

Tóm tắt

AbstractLiver cell death induced by stresses such as ischemia‐reperfusion, cholestasis and drug toxicity can trigger a sterile inflammatory response with activation of innate immune cells through release of damage‐associated molecular patterns (DAMPs). A similar inflammatory response can be induced by pathogen‐associated molecular patterns (PAMPs) such as endotoxin. Both DAMPs and PAMPs activate through toll‐like receptors the resident macrophages (Kupffer cells) and recruit activated neutrophils and monocytes into the liver. Central to this inflammatory response is promotion of reactive oxygen species (ROS) formation by these phagocytes. ROS are the principal toxic mediators by which inflammatory cells kill their targets, e.g. bacteria during host defense but also hepatocytes and other liver cells. The mechanism of ROS‐induced cell killing during inflammation involves the promotion of mitochondrial dysfunction through an intracellular oxidant stress in hepatocytes leading mainly to oncotic necrosis and less apoptosis. The additional release of cell contents amplifies the inflammatory injury. However, an inflammatory oxidant stress insufficient to directly cause cell damage can induce transcription of stress defence genes including antioxidant genes. This preconditioning effect of ROS enhances the resistance against future inflammatory oxidant stress and promotes the initiation of tissue repair processes. Despite the substantial progress in our understanding of mechanisms of inflammatory liver injury during the last decade, more research is necessary to better understand the role of ROS in acute liver inflammation and to develop clinically applicable therapeutic strategies that selectively target the detrimental effects of oxidant stress without compromising the vital function of ROS in host defense.

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Tài liệu tham khảo

10.1152/ajpgi.00568.2005

10.1096/fasebj.4.15.2253850

10.1002/hep.1840170523

Jaeschke H, 1991, Neutrophil‐induced liver cell injury in endotoxin shock is a CD11b/CD18‐dependent mechanism, Am. J. Physiol., 261, G1051

10.1053/jhep.2003.50341

10.1016/S0741-8329(02)00206-9

10.1002/hep.21425

Vedder NB, 1989, Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock, Surgery., 106, 509

Jaeschke H, 1991, Neutrophil and Kupffer cell‐induced oxidant stress and ischemia‐reperfusion injury in rat liver, Am. J. Physiol., 260, G355

10.1097/00024382-199501000-00010

Jaeschke H, 1992, Enhanced sinusoidal glutathione efflux during endotoxin‐induced oxidant stress in vivo, Am. J. Physiol., 263, G60

10.1002/hep.1840080420

10.1016/0016-5085(85)90218-5

10.1152/ajpgi.00342.2002

10.1002/hep.1840100307

10.1038/nature00858

10.1189/jlb.0306164

10.1189/jlb.1008585

10.1053/j.gastro.2006.01.038

10.1084/jem.20042614

10.4049/jimmunol.178.10.6573

10.4049/jimmunol.173.12.7115

10.1002/hep.23365

Jaeschke H, 1993, Complement activates Kupffer cells and neutrophils during reperfusion after hepatic ischemia, Am. J. Physiol., 264, G801

10.1152/ajpgi.2001.281.5.G1188

10.1111/j.1478-3231.2010.02284.x

10.1002/jlb.48.2.123

Chosay JG, 1997, Neutrophil margination and extravasation in sinusoids and venules of liver during endotoxin‐induced injury, Am. J. Physiol., 272, G1195

Jaeschke H, 1998, Activation of caspase 3 (CPP32)‐like proteases is essential for TNF‐alpha‐induced hepatic parenchymal cell apoptosisand neutrophil‐mediated necrosis in a murine endotoxin shock model, J. Immunol., 160, 3480, 10.4049/jimmunol.160.7.3480

10.1002/hep.510290222

10.1152/ajpgi.00287.2003

10.1152/ajpgi.00318.2003

10.1016/S0016-5085(99)70461-0

10.1016/j.ajpath.2010.11.026

10.1002/hep.1840080324

10.3109/10715769109105223

Liu P, 1994, Beneficial effects of extracellular glutathione against endotoxin‐induced liver injury during ischemia and reperfusion, Circ. Shock., 43, 64

10.1159/000064415

10.1002/jlb.52.4.377

10.1152/ajpgi.00141.2005

10.1002/jlb.61.6.647

Shappell SB, 1990, Mac‐1 (CD11b/CD18) mediates adherence‐dependent hydrogen peroxide production by human and canine neutrophils, J. Immunol., 144, 2702, 10.4049/jimmunol.144.7.2702

10.1046/j.1440-1746.2000.02207.x

10.1002/hep.1840080211

10.1016/S0891-5849(97)00084-1

10.1097/00024382-200304000-00009

10.1053/jhep.2003.50064

10.1111/j.1365-2796.2005.01476.x

10.1097/TP.0b013e3181d45a98

10.1056/NEJM198902093200606

10.1016/B978-0-08-046884-6.01012-5

10.1016/0006-2952(81)90576-1

10.1093/toxsci/kfq208

10.1016/S0014-5793(03)00235-7

10.1016/0891-5849(94)90191-0

10.1093/toxsci/kfg220

10.1111/j.1440-1746.2006.04646.x

10.1053/jhep.2003.50233

10.1016/j.jhep.2005.07.034

10.1152/ajpcell.1997.272.4.C1286

10.1152/ajpgi.90435.2008

Smith CV, 1987, Evidence for participation of lipid peroxidation and iron in diquat‐induced hepatic necrosis in vivo, Mol. Pharmacol., 32, 417

10.1053/jhep.2001.22002

10.1002/hep.1840400431

10.1053/gast.1996.v110.pm8566604

10.1002/hep.22498

10.1074/jbc.272.38.23707

10.1016/0168-8278(91)90868-C

10.1172/JCI114472

10.1016/S0168-8278(03)00415-X

10.1146/annurev.pharmtox.46.120604.141046

Tsuchihashi S, 2004, Heme oxygenase system in ischemia and reperfusion injury, Ann. Transplant., 9, 84

10.1016/j.taap.2006.04.010

10.1189/jlb.0308173

10.1111/j.1478-3231.2009.01979.x

10.1002/hep.20035

He S, 2009, A complement‐dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice, J. Clin. Invest., 119, 2304

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Journal of Gastroenterology and Hepatology (Australia)

Tập 26 Số s1

173-179

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