The role of HMGB-1 on the development of necrosis during hepatic ischemia and hepatic ischemia/reperfusion injury in mice

Watanabe, Taiji; Kubota, Sunao; Nagaya, Masaki; Ozaki, Shoichi; Nagafuchi, Hiroko; Akashi, Katsuya; Taira, Yasuhiko; Tsukikawa, Satoshi; Oowada, Shigeru; Nakano, S

doi:10.1016/j.jss.2004.10.019

Cited by 84 publications

(75 citation statements)

References 22 publications

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“…HMGB1 can activate inflammatory pathways when released from ischemic cells, and studies indicate that HMGB1 acts as an early mediator of inflammation and organ damage in hepatic I/R injury. HMGB1 levels were increased during liver I/R as early as 1 h after reperfusion and then further increased, in a time-dependent manner, up to 24 h. Inhibition of HMGB1 activity with a neutralizing antibody significantly decreased liver damage after I/R, whereas administration of recombinant HMGB1 worsened I/R injury [21,22] . Moreover, HMGB1 is massively released extracellularly and plays a cytokine-like function in the postischemic brain [11,12] .…”

Section: Discussionmentioning

confidence: 97%

Glycyrrhizin attenuates rat ischemic spinal cord injury by suppressing inflammatory cytokines and HMGB1

Gong

Yuan

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the neuroprotective effect of glycyrrhizin (Gly) against the ischemic injury of rat spinal cord and the possible role of the nuclear protein high-mobility group box 1 (HMGB1) in the process. Methods: Male Sprague-Dawley rats were subjected to 45 min aortic occlusion to induce transient lumbar spinal cord ischemia. The motor functions of the animals were assessed according to the modified Tarlov scale. The animals were sacrificed 72 h after reperfusion and the lumbar spinal cord segment (L2-L4) was taken out for histopathological examination and Western blotting analysis. Serum inflammatory cytokine and HMGB1 levels were analyzed using ELISA. Results: Gly (6 mg/kg) administered intravenously 30 min before inducing the transient lumbar spinal cord ischemia significantly improved the hind-limb motor function scores, and reduced the number of apoptotic neurons, which was accompanied by reduced levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the plasma and injured spinal cord. Moreover, the serum HMGB1 level correlated well with the serum TNF-α, IL-1β and IL-6 levels during the time period of reperfusion. Conclusion:The results suggest that Gly can attenuate the transient spinal cord ischemic injury in rats via reducing inflammatory cytokines and inhibiting the release of HMGB1.

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Section: Discussionmentioning

confidence: 97%

Glycyrrhizin attenuates rat ischemic spinal cord injury by suppressing inflammatory cytokines and HMGB1

Gong

Yuan

et al. 2011

Acta Pharmacol Sin

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“…In comparison with cold ischemia in liver transplantation, the 60-to 75-minute warm ischemia time used in experimental studies 17,18 is very robust. After warm liver I/R injury, both liver tissue 17,18 and bloodstream 18 HMGB1 levels increase in a time-dependent manner up to 24 hours, reflecting ongoing cellular damage and escalating inflammation. In contrast, we have reported that HMGB1 levels begin to decrease progressively within 1 to 2 hours after reperfusion, indicating that both ischemic damage and inflammatory response are limited after cold ischemia.…”

Section: Discussionmentioning

confidence: 99%

“…In murine models of warm segmental hepatic ischemia, HMGB1 levels increase rapidly after reperfusion. 17,18 Furthermore, HMGB1 blockade protects against warm hepatic I/R injury. Anti-HMGB1 antibody decreases hepatic cytokine expression and hepatocellular damage through TLR4-dependent mechanisms 17 and improves survival.…”

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confidence: 99%

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High mobility group box 1 protein as a marker of hepatocellular injury in human liver transplantation

et al. 2008

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High mobility group box 1 protein (HMGB1), a cytokine actively secreted by phagocytes and passively released from necrotic cells, is an inflammatory mediator in experimental hepatic ischemia/reperfusion injury. We characterized its expression in human liver transplantation. In 20 patients, in addition to systemic samples, blood was drawn from portal and hepatic veins during and after reperfusion to assess changes within the graft. Plasma HMGB1, tumor necrosis factor ␣ (TNF-␣), and interleukin-6 (IL-6) levels were measured, and HMGB1 immunohistochemistry was performed on biopsies taken before and after reperfusion. Plasma HMGB1 was undetectable before reperfusion, and levels in systemic circulation peaked after graft reperfusion. At portal declamping, HMGB1 levels were substantially higher in the caval effluent [188 (80-371) ng/mL] than in portal venous blood [0 (0-3) ng/mL, P Ͻ 0.001]. HMGB1 release from the graft continued thereafter. HMGB1 levels were not related to TNF-␣ or IL-6 levels. HMGB1 expression was up-regulated in biopsies taken after reperfusion (P ϭ 0.020), with intense hepatocyte and weak neutrophil staining. HMGB1 levels in hepatic venous blood correlated with graft steatosis (r ϭ 0.497, P ϭ 0.03) and peak postoperative alanine aminotransferase levels (r ϭ 0.588, P ϭ 0.008). Our results indicate that HMGB1 originates from the graft and is a marker of hepatocellular injury in human liver transplantation. Liver Transpl 14: 1517Transpl 14: -1525Transpl 14: , 2008

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“…In contrast, HMGB1 is released as an early mediator of inflammation and organ damage in hepatic IR injury (Tsung et al 2005). Inhibition of HMGB1 decreases the damage in hepatic IR injury (Tsung et al 2005;Watanabe et al 2005;Izuishi et al 2006). Additionally, binding of ART-123 to HMGB1 allows for the inhibition of the amplification of inflammatory response (Abeyama et al 2005;Ito et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Soluble Thrombomodulin Ameliorates Ischemia-Reperfusion Injury of Liver Grafts by Modulating the Proinflammatory Role of High-Mobility Group Box 1

Kashiwadate

Miyagi

Hara

et al. 2016

Tohoku J. Exp. Med.

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Transplantation using grafts obtained after cardiac death (CD) is considered a promising solution for graft shortages. However, no standard criteria for organ preservation have been established for CD donors. High-mobility group box 1 (HMGB1) is a DNA-binding protein that is released from dying hepatocytes as an early mediator of inflammation and organ tissue damage. HMGB1 stimulates immunocytes to produce inflammatory cytokines, thereby amplifying the inflammatory response. Thrombomodulin is an integral membrane protein that functions as an endothelial anticoagulant cofactor, and it binds HMGB1 through the extracellular domain. We investigated the effects of ART-123, recombinant human soluble thrombomodulin, on warm ischemia-reperfusion injury in liver grafts. Male Wistar rats were divided into four ex vivo groups: heart-beating (HB) group, in which livers were isolated from HB donors; CD group, in which livers were isolated from CD donors exposed to apnea-induced conditions and warm ischemic conditions for 30 min after cardiac arrest; and two CD groups pretreated with ART-123 (1 or 5 mg/kg). Each isolated liver was reperfused for 1 h after cold preservation for 6 h. The perfusate levels of HMGB1, LDH, TNF-α, and IL-6 were significantly lower in the CD group pretreated with ART-123 (5 mg/kg) than in the CD group. Bile production was significantly higher in the CD group pretreated with ART-123 (5 mg/kg) than in the CD group. The sinusoidal spaces were significantly narrower in the CD group than in the other groups. We propose that ART-123 maintains sinusoidal microcirculation by reducing endothelial cell damage during warm ischemia-reperfusion injury.

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The role of HMGB-1 on the development of necrosis during hepatic ischemia and hepatic ischemia/reperfusion injury in mice

Cited by 84 publications

References 22 publications

Glycyrrhizin attenuates rat ischemic spinal cord injury by suppressing inflammatory cytokines and HMGB1

Glycyrrhizin attenuates rat ischemic spinal cord injury by suppressing inflammatory cytokines and HMGB1

High mobility group box 1 protein as a marker of hepatocellular injury in human liver transplantation

Soluble Thrombomodulin Ameliorates Ischemia-Reperfusion Injury of Liver Grafts by Modulating the Proinflammatory Role of High-Mobility Group Box 1

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