Inflammatory genes in rat livers from cardiac- and brain death donors

Saat, Tanja C.; Susa, Denis; Kok, Niels F. M.; Engel, Sandra van den; Roest, Henk P.; Laan, Luc J. W. van der; IJzermans, Jan N.M.; Bruin, Ron W. F. de

doi:10.1016/j.jss.2015.04.057

Cited by 12 publications

(10 citation statements)

References 43 publications

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“…Similar findings were obtained from a previous study in which remote ischemic conditioning induced a significant elevation in serum IL-10 levels in a murine sepsis model which was associated with reduced inflammatory responses and better survival [ 42 ]. MCP-1 has multiple effects (chemokine for monocytes, contributing to apoptosis and biliary fibrosis) [ 43 ]. In a previous study significantly higher MCP-1 levels were found on the first postoperative day in patients who developed early graft dysfunction within the first week post-transplantation [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation

et al. 2018

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BackgroundIschemic-reperfusion (IR) injury still represents a major concern in clinical transplantation, especially in the era of extreme organ shortage and extended criteria donor organs. In the present study we aimed to investigate the hepatoprotective effects of remote ischemic conditioning (RIC) in a rat model of arterialized orthotopic liver transplantation (OLT).MethodsMale Lewis rats were used (n = 144 / 72 OLT cases; 240–340g) as donors and recipients. Livers were flushed and stored in 4°C HTK-solution for 8h before implantation. Recipients were randomly allocated into three experimental groups: RIC 1, RIC 2, Control. In RIC 1, RIC 2 groups, RIC was applied in the recipient before hepatectomy or after reperfusion (4x5-5min IR via clamping the infrarenal aorta), respectively. Animals were sacrificed at 1, 3, 24, 168h post-reperfusion (n = 6 recipient/group/time point). Hepatocellular injury, graft circulation, serum cytokines, tissue redox-stress and adenosine-triphosphate (ATP) levels have been assessed. Additional markers were analyzed, using Western blotting and reverse-transcription polymerase chain reaction.ResultsRIC 1 group showed significantly (p<0.05) improved portal venous and microcirculation flow as well as velocity. RIC has significantly reduced tissue injury according to the serum levels of transaminases and results of histopathological evaluation. Reduced TUNEL-staining (p<0.01 RIC 1–2 vs. Control) and elevated pBAD/BAD ratio was detected in the RIC groups (p<0.01 RIC 1 vs. Control). Supporting findings were obtained from measurements of serum IL-10 as well as tissue malondialdehyde and ATP levels. Hemoxygenase-1 (HO-1) mRNA-expression was significantly higher in RIC 1 compared to Control (p<0.05 RIC 1 vs. Control).ConclusionThese results suggest that RIC might confer potent protection against the detrimental effects of IR injury including tissue damage, apoptosis, graft circulation, inflammation, tissue energetic status in OLT. HO-1 overexpression might play an orchestrating role in RIC mediated organ protection. An earlier intervention (RIC 1 protocol) was more effective than remote conditioning after graft reperfusion.

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Section: Discussionmentioning

confidence: 99%

Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation

et al. 2018

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“…Once released in the extracellular space, the protein can bind to PRRs such as RAGE, TLR2, TLR4, and TLR9, thereby mediating and promoting tissue inflammation. Convincing evidence has shown that HMGB1 is generated in organs upon IRI including human kidney allografts (435,468,605,617,624,639,720), but also emitted upon brain death (282,322,555,702). In fact, it appears that oxidative stress is a central regulator of HMGB1's translocation, release, and activity in sterile inflammation and cell death including necrosis, apoptosis, autophagic cell death, and pyroptosis (720).…”

Section: Class Ia/ib Dampsmentioning

confidence: 99%

Origin and Consequences of Necroinflammation

Sarhan

Land

Tonnus

et al. 2018

Physiological Reviews

165

152

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When cells undergo necrotic cell death in either physiological or pathophysiological settings in vivo, they release highly immunogenic intracellular molecules and organelles into the interstitium and thereby represent the strongest known trigger of the immune system. With our increasing understanding of necrosis as a regulated and genetically determined process (RN, regulated necrosis), necrosis and necroinflammation can be pharmacologically prevented. This review discusses our current knowledge about signaling pathways of necrotic cell death as the origin of necroinflammation. Multiple pathways of RN such as necroptosis, ferroptosis, and pyroptosis have been evolutionary conserved most likely because of their differences in immunogenicity. As the consequence of necrosis, however, all necrotic cells release damage associated molecular patterns (DAMPs) that have been extensively investigated over the last two decades. Analysis of necroinflammation allows characterizing specific signatures for each particular pathway of cell death. While all RN-pathways share the release of DAMPs in general, most of them actively regulate the immune system by the additional expression and/or maturation of either pro- or anti-inflammatory cytokines/chemokines. In addition, DAMPs have been demonstrated to modulate the process of regeneration. For the purpose of better understanding of necroinflammation, we introduce a novel classification of DAMPs in this review to help detect the relative contribution of each RN-pathway to certain physiological and pathophysiological conditions.

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“…In fact, documented parameters involved in BD‐activated innate immune events include DAMPs , upregulated PRRs and signaling molecules , complement fragments , cytokines such as IL‑1β , and upregulated chemokine receptors . Moreover, mature activated DCs could also be demonstrated in the blood and spleen of brain‐dead organ donors (Table ) .…”

Section: Donor Bd: Oxidative Stress‐mediated Activation Of the Innatementioning

confidence: 99%

“…Class Ia DAMPs such as HMGB1 and HSPs are generated in reperfusion‐injured organs including human renal allografts , but also emitted under BD conditions . These molecules considerably contribute to creation of sterile inflammation including IRI‐mediated inflammation when sensed by those members of the NLR or ALR family that form inflammasomes .…”

Section: A Plethora Of Damps and An Attempt To Classify Themmentioning

confidence: 99%

Transplantation and Damage-Associated Molecular Patterns (DAMPs)

Land

Agostinis

Gasser

et al. 2016

American Journal of Transplantation

133

110

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Upon solid organ transplantation and during cancer immunotherapy, cellular stress responses result in the release of damage-associated molecular patterns (DAMPs). The various cellular stresses have been characterized in detail over the last decades, but a unifying classification based on clinically important aspects is lacking. Here, we provide an in-depth review of the most recent literature along with a unifying concept of the danger/injury model, suggest a classification of DAMPs, and review the recently elaborated mechanisms that result in the emission of such factors. We further point out the differences in DAMP responses including the release following a heat shock pattern, endoplasmic reticulum stress, DNA damage-mediated DAMP release, and discuss the diverse pathways of regulated necrosis in this respect. The understanding of various forms of DAMPs and the consequences of their different release patterns are prerequisite to associate serum markers of cellular stresses with clinical outcomes.

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Inflammatory genes in rat livers from cardiac- and brain death donors

Cited by 12 publications

References 43 publications

Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation

Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation

Origin and Consequences of Necroinflammation

Transplantation and Damage-Associated Molecular Patterns (DAMPs)

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