Interleukin-6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice

Zhang, Xiuying; Tachibana, Shunsuke; Wang, Hua; Hisada, Masayuki; Williams, G. M.; Gao, Bin; Sun, Zhaoli

doi:10.1002/hep.23909

Cited by 65 publications

(51 citation statements)

References 45 publications

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“…[28] On the other hand, IL-6 knockout mice fed chronic alcohol showed increased liver fat accumulation, lipid peroxidation, mitochondrial DNA damage, and sensitization of hepatocytes to TNF-α induced apoptosis, which was prevented by the administration of recombinant IL-6. [29] These findings suggest that IL-6 has a protective effect at the early phase of ALD. Furthermore, IL-17 can act with other cytokines to activate NF-kB which plays a central role in regulating genetic transcription and encoding of inflammatory cytokines, and induce IL-8.…”

Section: Structural Organization Of the Liver And Cytokines Potentialmentioning

confidence: 84%

Physiological potential of cytokines and liver damages

Mannaa¹,

Abdel-Wahhab²

2016

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Cytokines are soluble extracellular small molecular weight protein or peptide. They are produced by virtually every nucleated cell type in response to injurious stimuli to control body metabolism, infection, inflammation and tissue or neuronal damage; therefore acting as messengers between tissues and the immune system; and participating in many physiological processes through their either anti-inflammatory or pro-inflammatory characteristics. Many cytokines have multiple cellular sources and targets, as well as many natural inducers and inhibitors. In pathophysiological conditions and during the early phase of chronic liver diseases, agent like virus, bacteria, parasites, ethanol, or toxins, induce secretion of cytokines at high levels. The presence of cytokine antagonists and soluble cytokine receptors, often released in concert with their respective cytokine agonist, presents additional complexity to interpretation.

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Section: Structural Organization Of the Liver And Cytokines Potentialmentioning

confidence: 84%

Physiological potential of cytokines and liver damages

Mannaa¹,

Abdel-Wahhab²

2016

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“…It has been reported that IL-6 prevents fatty liver transplantation failure by improving microcirculation, 61 and that it protects against mitochondrial DNA damage in the liver. 62 TNF-␣, however, plays paradoxical dual roles in both prevention and promotion of IRI in the liver tissue. Recent reports indicate that inhibiting TNF-␣ production improves donor livers.…”

Section: Discussionmentioning

confidence: 99%

The Protective Role of CD59 and Pathogenic Role of Complement in Hepatic Ischemia and Reperfusion Injury

Zhang

Xing

et al. 2011

The American Journal of Pathology

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Hepatic ischemia-reperfusion injury (IRI) is a major factor influencing graft outcome in liver transplantation, but its mechanism is not well defined. Although complement, including the membrane attack complex (MAC), a terminal product of complement activation, is thought to be involved in the multiple reactions subsequent to the ischemia-reperfusion (IR) process, the role of MAC in the pathogenesis of hepatic IRI requires further investigation. We used a warm ischemia-reperfusion injury model in mice and a syngeneic orthotopic liver transplantation model in rats to define the role of complement, including MAC, in hepatic IR. CD59-deficient mice had more severe liver dysfunction, evidenced by increased aspartate aminotransferase levels and increased injury of liver parenchymal and nonparenchymal cells than did CD59-sufficient mice during warm hepatic IR. Furthermore, complement depletion in CD59-deficient mice by pretreatment with cobra venom factor (CVF) or the genetic introduction of C3 deficiency partially protected against development of the severe liver dysfunction that occurred in CD59-deficient mice. Severity of liver dysfunction correlated with MAC deposition, apoptotic cells, and increased inflammatory mediators such as tumor necrosis factor ␣. Liver transplantation is a routine and powerful approach for treatment of patients with acute or chronic liver failure of various causes. 1 Nevertheless, hepatic ischemia-reperfusion (IR) remains a major deleterious factor influencing graft outcome in organ transplantation. The incidence of primary graft failure (5% to 15%) and initial poor function (10% to 25%) is strongly dependent on the extent of ischemia-reperfusion injury (IRI). 2-4 IRI also initiates later graft failure by triggering irreversible intrahepatic biliary tract injury (ischemic-type biliary lesion) or by promoting rejection through activation of innate immunity. 5 At present, because of the shortage of organs for transplantation, the donor pool has been expanded by utilization of marginal organs from old donors or non-heart-beating donors, as well as grafts with prolonged cold storage, and even allografts donated after cardiac death. It is conceivable that grafts from such donors could cause severe liver injury, because they have usually experienced a long ischemia time. To improve the outcome of liver transplantation, therefore, it is imperative to better understand the mechanisms involved in IRI and to design novel therapeutic strategies for prevention of IRI.Ischemia-reperfusion injury is characterized by the presence of activated polymorphonuclear leukocytes, oxygen radical formation, 6 and cytokine release. 7,8 The process that temporarily blocks blood supply followed by blood reperfusion to the living donor after the transplantation causes attraction, activation, adhesion, and migration of neutrophils at the site of donor organ, thereby

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“…Some studies of alcohol feeding in mice have hinted that mitochondrial alterations may occur as the liver adapts to alcohol. One study showed some enhancement of mitochondrial respiration in the liver of mice fed alcohol orally (20), whereas another study found that alcohol feeding to mice increases complex I levels in liver mitochondria (21). These studies suggest that chronic alcohol feeding to mice may trigger mitochondrial alterations as an adaptive response, which needs to be further explored.…”

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confidence: 99%