Activation of Human Umbilical Vein Endothelial Cells Leads to Relocation and Release of High‐Mobility Group Box Chromosomal Protein 1

Mullins, G. E.; Sundén-Cullberg, Jonas; Johansson, Anne; Rouhiainen, Ari; Erlandsson-Harris, Helena; Yang, Huan; Tracey, Kevin J.; Rauvala, Heikki; Palmblad, Jan; Andersson, Jan; Treutiger, Carl-Johan

doi:10.1111/j.0300-9475.2004.01518.x

Cited by 134 publications

(114 citation statements)

References 31 publications

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“…Previous findings [28][29][30] support the idea that HMGB1 is released from endothelial cells. HMGB1 is translocated from the nucleus to the cytoplasm and released from the cell upon stimulation by LPS or TNF-a.…”

Section: Systemic Inflammation: Three Waves Of Danger Signalingsupporting

confidence: 59%

“…HMGB1 is translocated from the nucleus to the cytoplasm and released from the cell upon stimulation by LPS or TNF-a. 28 However, the release of HMGB1 from endothelial cells activated by either LPS or TNF-a is relatively slow. In contrast, in vivo intrarenal injection of uric acid, mimicking its postischemic surge, or renal ischemia-reperfusion insult lead to HMGB1 nucleocytoplasmic translocation and subsequent release from the cytosol into the circulation within 1 hour.…”

Section: Systemic Inflammation: Three Waves Of Danger Signalingmentioning

confidence: 99%

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Messengers without Borders

Ratliff

Rabadi

Vasko

et al. 2013

Journal of the American Society of Nephrology

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The list of signals sent by an injured organ to systemic circulation, so-called danger signals, is growing to include multiple metabolites and secreted moieties, thus revealing a highly complex and integrated network of interlinked systemic proinflammatory and proregenerative messages. Emerging new data indicate that, apart from the well established local inflammatory response to AKI, danger signaling unleashes a cascade of precisely timed, interdependent, and intensity-gradated mediators responsible for development of the systemic inflammatory response. This fledgling realization of the importance of the systemic inflammatory response to the localized injury and inflammation is at the core of this brief overview. It has a potential to explain the additive effects of concomitant diseases or preexisting chronic conditions that can prime the systemic inflammatory response and exacerbate it out of proportion to the actual degree of acute kidney damage. Although therapies for ameliorating AKI per se remain limited, a potentially powerful strategy that could reap significant benefits in the future is to modulate the intensity of danger signals and consequently the systemic inflammatory response, while preserving its intrinsic proregenerative stimuli.

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Section: Systemic Inflammation: Three Waves Of Danger Signalingsupporting

confidence: 59%

Section: Systemic Inflammation: Three Waves Of Danger Signalingmentioning

confidence: 99%

Messengers without Borders

Ratliff

Rabadi

Vasko

et al. 2013

Journal of the American Society of Nephrology

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“…HMGB1 may be released both through active secretion from various cells, including activated monocytes/macrophages, 9 neutrophils, 25 and endothelial cells, 26 and passively from necrotic cells. 5 Both mechanisms likely contribute to the described HMGB1 release from the graft during liver transplantation.…”

Section: Discussionmentioning

confidence: 99%

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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“…81 There is one report, not yet confirmed, that cultured EC will secrete HMGB1 in response to TNF, but injury was not assessed in this study. 82 In MØs, secretion of HMGB1 involves hyperacetylation of the protein whereas release by injury does not. 83 HMGB1 has been shown to favor murine T H 1 differentiation.…”

Section: Il-12 Has Emerged As a Key Initiator Of Ifn-␥ Responses By Bmentioning

confidence: 99%

Interferon-γ Axis in Graft Arteriosclerosis

Tellides

Pober

2007

Circulation Research

104

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Abstract-Cardiac transplantation is the most effective treatment for advanced heart failure. Despite improvements in immunosuppression therapy that prevent acute rejection, cardiac allografts fail at rates of 3% to 5% per posttransplant year. The hallmark morphological lesion of chronically failing cardiac allografts, also seen in chronic renal and liver graft failure, is luminal stenosis of blood vessels, especially of conduit arteries. Late graft failure results from widespread secondary ischemic injury to the graft parenchyma rather than direct immune-mediated damage. Although this process affects the entire graft vasculature, graft arteriosclerosis is a suitable term to describe the problem because it applies to different types of failing organs and because it emphasizes the central feature, namely an accelerated form of arterial injury and remodeling. The precise pathogenesis of graft arteriosclerosis is unknown. In this review, we make the case that the signature T-helper type 1 cytokine, interferon (IFN)-␥, is a key effector in graft arteriosclerosis, which, together with the IFN-␥-inducing cytokine interleukin-12 and IFN-␥-inducible chemokines such as CXCR3 ligands, constitute a positive feedback loop for T-cell activation, differentiation, and recruitment that we refer to as the IFN-␥ axis. We evaluate the evidence to support this hypothesis in clinical observational and experimental animal studies. Additionally, we examine the regulation of IFN-␥ production within the artery wall, the effects of IFN-␥ on vessel wall cells, and the outcome of therapeutic agents on IFN-␥ production and signaling. These observations lead us to suggest that new therapies for graft arteriosclerosis should be optimized which focus on reducing IFN-␥ synthesis or actions. (Circ Res. 2007;100:622-632.)

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Activation of Human Umbilical Vein Endothelial Cells Leads to Relocation and Release of High‐Mobility Group Box Chromosomal Protein 1

Cited by 134 publications

References 31 publications

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

Interferon-γ Axis in Graft Arteriosclerosis

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