Innate Immune Regulations and Liver Ischemia-Reperfusion Injury

Lü, Ling; Zhou, Haoming; Ni, Ming; Wang, Xuehao; Busuttil, Ronald W.; Kupiec‐Weglinski, Jerzy W.; Zhai, Yuan

doi:10.1097/tp.0000000000001411

Cited by 152 publications

(129 citation statements)

References 129 publications

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“…The liver comprises the highest content of tissueresident immune cells in the body, including Kupffer cells, dendritic cells, and natural killer cells. (17) These immune cells function together with infiltrating myeloid and lymphoid cells to respond to PAMPs and DAMPs. Thus, it is not surprising that the liver reacts vividly to systemic inflammation.…”

Section: Systemic Inflammatory Responsementioning

confidence: 99%

The Role of Complement in Liver Injury, Regeneration, and Transplantation

et al. 2019

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The liver is both an immunologically complex and a privileged organ. The innate immune system is a central player, in which the complement system emerges as a pivotal part of liver homeostasis, immune responses, and crosstalk with other effector systems in both innate and adaptive immunity. The liver produces the majority of the complement proteins and is the home of important immune cells such as Kupffer cells. Liver immune responses are delicately tuned between tolerance to many antigens flowing in from the alimentary tract, a tolerance that likely makes the liver less prone to rejection than other solid organ transplants, and reaction to local injury, systemic inflammation, and regeneration. Notably, complement is a double‐edged sword as activation is detrimental by inducing inflammatory tissue damage in, for example, ischemia–reperfusion injury and transplant rejection yet is beneficial for liver tissue regeneration. Therapeutic complement inhibition is rapidly developing for routine clinical treatment of several diseases. In the liver, targeted inhibition of damaged tissue may be a rational and promising approach to avoid further tissue destruction and simultaneously preserve beneficial effects of complement in areas of proliferation. Here, we argue that complement is a key system to manipulate in the liver in several clinical settings, including liver injury and regeneration after major surgery and preservation of the organ during transplantation.

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Section: Systemic Inflammatory Responsementioning

confidence: 99%

The Role of Complement in Liver Injury, Regeneration, and Transplantation

et al. 2019

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“…Release of inflammatory cytokines and chemokines results in activation of neutrophils and macrophages, promoting tissue destruction. Lipid peroxidation, ROS and release of damage‐associated molecular patterns (DAMPS) during hepatocyte injury amplify the destructive activity of neutrophils and macrophages …”

Section: Introductionmentioning

confidence: 99%

Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

Dar

Sullivan

Bynon

et al. 2019

Liver International

274

245

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Liver disease causing end organ failure is a growing cause of mortality. In most cases, the only therapy is liver transplantation. However, liver transplantation is a complex undertaking and its success is dependent on a number of factors. In particular, liver transplantation is subject to the risks of ischaemia‐reperfusion injury (IRI). Liver IRI has significant effects on the function of a liver after transplantation. The cellular and molecular mechanisms governing IRI in liver transplantation are numerous. They involve multiple cells types such as liver sinusoidal endothelial cells, hepatocytes, Kupffer cells, neutrophils and platelets acting via an interconnected network of molecular pathways such as activation of toll‐like receptor signalling, alterations in micro‐RNA expression, production of ROS, regulation of autophagy and activation of hypoxia‐inducible factors. Interestingly, the cellular and molecular events in liver IRI can be correlated with clinical risk factors for IRI in liver transplantation such as donor organ steatosis, ischaemic times, donor age, and donor and recipient coagulopathy. Thus, understanding the relationship of the clinical risk factors for liver IRI to the cellular and molecular mechanisms that govern it is critical to higher levels of success after liver transplantation. This in turn will help in the discovery of therapeutics for IRI in liver transplantation – a process that will lead to improved outcomes for patients suffering from end‐stage liver disease.

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“…Indeed, hypoxia activates multiple hypoxia mediators and in turn accelerate or antagonize hepatic damage [1, 2]. A variety of pharmacological interventions have been proposed to alleviate hypoxic injury in the liver, however, there is no promising therapy for the prevention and treatment of hypoxic liver injury yet [3-6].…”

Section: Introductionmentioning

confidence: 99%

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Zhi

Shao

Xue

et al. 2017

Cell Physiol Biochem

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Background/Aims: Hypoxic/ischemic injury to the liver is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ ischemic events, and δ-opioid receptor (DOR) is protective against hypoxic/ischemic injury, we asked if pharmacological activation of DOR can alter hypoxic events by regulating miRNA expression in the liver. As the first step, the present work aimed at testing the effect of DOR activation on hepatic miRNA expression in hypoxia. Methods: Male Sprague Dawley rats were exposed to hypoxia (9.5-10% O₂) for 1, 5, or 10 days with or without DOR activation. The target miRNAs were selected according to TaqMan low-density array (TLDA) data and analyzed by quantitative real-time PCR. Results: We found that: 1) 1-day hypoxia caused the upregulation of 9 miRNAs (miR-7a-5p, miR-10a-5p, miR-25-3p, miR-26b-5p, miR-122-5p, miR-128a-3p, miR-135b-5p, miR-145-5p, and miR-181a-5p) and the downregulation of 2 miRNAs (miR-34a-5p and miR-182); 2) 5 and 10-days hypoxia altered the expression of 4 miRNAs (miR-34c-5p, miR-184, miR-107-3p and miR192-5p); 3) DOR activation shifted the expression of 8 miRNAs (miR-122-5p, miR-146a-5p, miR-30e-5p, miR-128a-3p, miR-182, miR-192-5p miR-107-3p and miR-184) in normoxic condition; and 4) DOR activation modified hypoxia-induced changes in 6 miRNAs (miR-142-5p, miR-145-5p, miR-146a-5p, miR-204-5p, miR-34a-5p and miR-192-5p). Conclusion: Hypoxia significantly modifies the miRNA profile in the liver, while DOR activation can modify the hypoxic modification. Therefore, it is potentially possible to alter hypoxic/ischemic pathophysiology in the liver through DOR pharmacotherapy.

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Innate Immune Regulations and Liver Ischemia-Reperfusion Injury

Cited by 152 publications

References 129 publications

The Role of Complement in Liver Injury, Regeneration, and Transplantation

The Role of Complement in Liver Injury, Regeneration, and Transplantation

Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

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