HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure
Acute liver failure (ALF) is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF) and sepsis; however, the underlyi...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/5928078 |
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| author | Runkuan Yang Xiaoping Zou Jyrki Tenhunen Tor Inge Tønnessen |
| author_facet | Runkuan Yang Xiaoping Zou Jyrki Tenhunen Tor Inge Tønnessen |
| author_sort | Runkuan Yang |
| collection | DOAJ |
| description | Acute liver failure (ALF) is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF) and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT). BT triggers/induces systemic inflammatory responses syndrome (SIRS), which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF. |
| format | Article |
| id | doaj-art-2db25ba19b9c4f26829615ce6e84dd13 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-2db25ba19b9c4f26829615ce6e84dd132025-02-03T05:44:26ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/59280785928078HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver FailureRunkuan Yang0Xiaoping Zou1Jyrki Tenhunen2Tor Inge Tønnessen3Department of Intensive Care Medicine, Tampere University Hospital, University of Tampere, 10 Bio Katu, 33014 Tampere, FinlandDepartment of Gastroenterology, Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Street, Nanjing 210008, ChinaDepartment of Intensive Care Medicine, Tampere University Hospital, University of Tampere, 10 Bio Katu, 33014 Tampere, FinlandDepartment of Emergencies and Critical Care, Oslo University Hospital, P.O. Box 4950 Nydalen, 0424 Oslo, NorwayAcute liver failure (ALF) is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF) and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT). BT triggers/induces systemic inflammatory responses syndrome (SIRS), which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF.http://dx.doi.org/10.1155/2017/5928078 |
| spellingShingle | Runkuan Yang Xiaoping Zou Jyrki Tenhunen Tor Inge Tønnessen HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure Mediators of Inflammation |
| title | HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure |
| title_full | HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure |
| title_fullStr | HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure |
| title_full_unstemmed | HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure |
| title_short | HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure |
| title_sort | hmgb1 and extracellular histones significantly contribute to systemic inflammation and multiple organ failure in acute liver failure |
| url | http://dx.doi.org/10.1155/2017/5928078 |
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