Diphenyleneiodonium ameliorates acute liver rejection during transplantation by inhibiting neutrophil extracellular traps formation in vivo

Liu, Yanyao; Qin, Xiaoyan; Lei, Zilun; Chai, Hao; Wu, Zhongjun

doi:10.1016/j.trim.2021.101434

Cited by 13 publications

(11 citation statements)

References 34 publications

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“…Therefore, elucidation of the mechanisms involved in AR development following liver transplantation will inform the development of new therapies as well as treatment strategies. Our previous study proved that excessive neutrophil accumulation or hyper-responsiveness of neutrophils and an uncontrolled NET formation process after liver transplantation highly correlated with the formation of the local liver inflammatory microenvironment and AR following liver transplantation (13,24). High-mobility group box 1 (HMGB1) is a damage-related molecular pattern molecule triggering the activation of macrophages in inflammatory microenvironments, resulting in tissue injury (25,26).…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps Regulate HMGB1 Translocation and Kupffer Cell M1 Polarization During Acute Liver Transplantation Rejection

Liu

Qin

et al. 2022

Front. Immunol.

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Neutrophil extracellular traps (NETs) play important roles in hepatic ischemic reperfusion injury (IRI) and acute rejection (AR)-induced immune responses to inflammation. After liver transplantation, HMGB1, an inflammatory mediator, contributes to the development of AR. Even though studies have found that HMGB1 can promote NET formation, the correlation between NETs and HMGB1 in the development of AR following liver transplantation has not been elucidated. In this study, levels of serum NETs were significantly elevated in patients after liver transplantation. Moreover, we found that circulating levels of NETs were negatively correlated with liver function. In addition, liver transplantation and elevated extracellular HMGB1 promoted NET formation. The HMGB1/TLR-4/MAPK signaling pathway, which is initiated by HMGB1, participates in NET processes. Moreover, in the liver, Kupffer cells were found to be the main cells secreting HMGB1. NETs induced Kupffer cell M1 polarization and decreased the intracellular translocation of HMGB1 by inhibiting DNase-1. Additionally, co-treatment with TAK-242 (a TLR-4 inhibitor) and rapamycin more effectively alleviated the damaging effects of AR following liver transplantation than either drug alone.

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Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps Regulate HMGB1 Translocation and Kupffer Cell M1 Polarization During Acute Liver Transplantation Rejection

Liu

Qin

et al. 2022

Front. Immunol.

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“…Studies have reported that tissue inhibitor of metalloproteinases-1, a physiological inhibitor of matrix metallopeptidase 9 (MMP9), can reduce the formation of NETs and thus limit the effect of NETs on the liver IRI ( 92 ). Diphenyleneiodonium (DPI), a NOX inhibitor, can inhibit the formation of NETs by inhibiting the NADPH/ROS/PAD4 signaling pathway, thereby reducing liver injury and maintaining liver function ( 137 ). Tetramethylpyrazine (TMP), the main chemical component of Ligusticum chuanxiong , inhibits NET formation during liver I/R by inhibiting NOX.…”

Section: Extracellular Traps In Organ Ischemia Reperfusion Injurymentioning

confidence: 99%

“…The inhibition of NET formation via the targeting of NET components could limit the role of NETs more directly. The blockade of ROS production using antibodies or the inhibition of citrullination histones with PAD4 inhibitors can inhibit NET formation and protect against IRI in the liver ( 90 , 137 , 138 , 190 ), kidneys ( 21 , 102 , 105 ), intestine ( 112 ), lungs ( 113 ), cerebrum ( 115 , 117 ), myocardium ( 120 ), limbs ( 128 ), and skin ( 129 ). The function of NETs largely depends on their reticular DNA structure and the various proteins embedded within them.…”

Section: Targeting Extracellular Traps For Ischemia Reperfusion Injur...mentioning

confidence: 99%

The role of extracellular traps in ischemia reperfusion injury

Zhang

et al. 2022

Front. Immunol.

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In response to strong signals, several types of immune cells release extracellular traps (ETs), which are web-like structures consisting of DNA decorated with various protein substances. This process is most commonly observed in neutrophils. Over the past two decades, ET formation has been recognized as a unique mechanism of host defense and pathogen destruction. However, the role of ETs in sterile inflammation has only been studied extensively in recent years. Ischemia reperfusion injury (IRI) is a type of sterile inflammatory injury. Several studies have reported that ETs have an important role in IRI in various organs. In this review, we describe the release of ETs by various types of immune cells and focus on the mechanism underlying the formation of neutrophil ETs (NETs). In addition, we summarize the role of ETs in IRI in different organs and their effects on tumors. Finally, we discuss the value of ETs as a potential therapeutic target for organ IRI and present possible challenges in conducting studies on IRI-related ETs as well as future research directions and prospects.

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“…However, there are insufficient studies to assess the correlation between NETs formation and AR after liver transplantation. As such, we have conducted some studies in this area ( 8 , 15 ). Serum samples obtained from 13 liver transplant individuals were analyzed, and we found that the levels of NETs were elevated.…”

Section: Nets and Acute Rejectionmentioning

confidence: 99%

“…Additionally, NETs are important in treating non-infectious diseases, such as cancer, diabetes, thrombosis, and autoimmune illnesses (4)(5)(6). Recent evidence suggests that NETs may contribute to pathological changes after liver transplantation, including liver ischemia-reperfusion injury (IRI), acute rejection, and recurrence of hepatocellular carcinoma (7)(8)(9). However, there is little knowledge of the relationship between NET formation and complications of liver transplantation.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil extracellular traps and complications of liver transplantation

et al. 2022

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Many end-stage liver disease etiologies are attributed to robust inflammatory cell recruitment. Neutrophils play an important role in inflammatory infiltration and neutrophil phagocytosis, oxidative burst, and degranulation. It has also been suggested that neutrophils may release neutrophil extracellular traps (NETs) to kill pathogens. It has been proven that neutrophil infiltration within the liver contributes to an inflammatory microenvironment and immune cell activation. Growing evidence implies that NETs are involved in the progression of numerous complications of liver transplantation, including ischemia-reperfusion injury, acute rejection, thrombosis, and hepatocellular carcinoma recurrence. NETs are discussed in this comprehensive review, focusing on their effects on liver transplantation complications. Furthermore, we discuss NETs as potential targets for liver transplantation therapy.

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Diphenyleneiodonium ameliorates acute liver rejection during transplantation by inhibiting neutrophil extracellular traps formation in vivo

Cited by 13 publications

References 34 publications

Neutrophil Extracellular Traps Regulate HMGB1 Translocation and Kupffer Cell M1 Polarization During Acute Liver Transplantation Rejection

Neutrophil Extracellular Traps Regulate HMGB1 Translocation and Kupffer Cell M1 Polarization During Acute Liver Transplantation Rejection

The role of extracellular traps in ischemia reperfusion injury

Neutrophil extracellular traps and complications of liver transplantation

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