Allograft Inflammatory Factor-1 is Up-regulated in Warm and Cold Ischemia-Reperfusion Injury in Rat Liver and May be Inhibited by FK506

Jiang, Weiwei; Kong, Lianbao; Wu, Xiaofeng; Pu, Liyong; Wang, Xuehao

doi:10.1016/j.jss.2009.05.038

Cited by 11 publications

(6 citation statements)

References 28 publications

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“…Idebenone56 and curcumin57 target these genes, and this probably accounts for their protection against IRI. Other hepatoprotective drugs that target the production of pro‐ or anti‐inflammatory cytokines (ie, IL‐1A, IL‐1B, and IL‐10) include adrenomedulin,58 transresveratrol,59 tacrolimus,60 and erythropoietin 17. This last molecule is part of the hypoxia‐related mechanisms that also involve VEGF.…”

Section: Discussionmentioning

confidence: 99%

Improving the function of liver grafts exposed to warm ischemia by the leuven drug protocol: Exploring the molecular basis by microarray

et al. 2012

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Livers exposed to warm ischemia (WI) before transplantation are at risk for primary nonfunction (PNF), graft dysfunction, and ischemic biliary strictures, all associated with ischemia/reperfusion injury (IRI). Our multifactorial approach, Leuven drug protocol (LDP), has been shown to reduce these effects and increase recipient survival in WI/IRI-damaged porcine liver transplantation. The aim was the identification of the molecular mechanisms responsible for the hepatoprotective effects of the LDP. Porcine livers were exposed to 45 minutes of WI, cold-stored for 4 hours, transplanted, and either modulated (LDP group; n ¼ 3) or not modulated (control group; n ¼ 4). In the LDP group, the donor livers were flushed with streptokinase and epoprostenol before cold perfusion; the recipients received intravenous glycine, a-1-acid-glycoprotein, FR167653 (a mitogen-activated protein kinase inhibitor), a-tocopherol, glutathione, and apotransferrin. Liver samples were taken before WI and 1 hour after reperfusion. Gene expression was determined with microarrays and molecular pathways and key regulatory genes were identified. The number of genes changed between baseline and 1 hour after reperfusion was 686 in the LDP group and 325 in the control group. The extra genes in the LDP group belonged predominantly to pathways related to cytokine activity, apoptosis, and cell proliferation. We identified 7 genes that were suppressed in the LDP group. These genes could be linked in part to the administered drugs. New potential drug targets were identified on the basis of genes induced in the control group but unaffected in the LDP group and interactions predicted by the literature. In

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Section: Discussionmentioning

confidence: 99%

Improving the function of liver grafts exposed to warm ischemia by the leuven drug protocol: Exploring the molecular basis by microarray

et al. 2012

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“…Recent studies reported that short-tion in both TLR-1 positive keratinocytes and dermal infiltrating cells, but have increased the dermal TLR-2 positive cells in atopic dermatitis (AD), affecting the inflammation associated with AD [34]. Although the role of TLRs was not discussed in the previous report [33], there is suggestive evidence that FK506 may inhibit the AIF-1 expression through the TLRs. In our study, the mRNA expression levels of TLR-2 and TLR-4 were increased after 30 minutes reperfusion, and the TLR4 expression level remained high after 60 minutes.…”

Section: Discussionmentioning

confidence: 98%

“…Autieri et al, have shown the impact of cell cycle deregulation in over expression of AIF-1, causing proliferation of vascular smooth muscle cells [16]. The AIF-1 expression level was shown to be upregulated in cardiac allograft after cold and warm IR and the expression was reduced with a low dose of FK506 pretreatment [33]. This finding suggests that the FK506 effect most likely was not on the recipient macrophages infiltrating the allograft, but was on donor organ tissue.…”

Section: Discussionmentioning

confidence: 99%

Allograft Inflammatory Factor-1 in Cardiac Ischemia Re-perfusion Injury: Release of Molecular Markers in an <i>in Vitro</i> Setting

McDaniel¹,

Zhou²,

Rigney³

et al. 2013

OJOTS

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Initial ischemia/reperfusion injury (IRI) may have an impact on recipient immune responses after transplantation. Allograft inflammatory factor-1 (AIF-1) has been implicated in the regulation of inflammation associated with organ rejection. We hypothesized that it is either passively released from injured tissues during organ procurement, or actively secreted by allograft infiltrating cells contributing to allograft dysfunction. We investigated the impact of IRI in an in vitro study of human heart tissue during the process of transplantation. The mRNA expression levels for both isoforms of the AIF-1, I2 and I3 were significantly increased after 30 minutes reperfusion (AIF-1 I2: p < 0.01 vs. AIF-1 I3: p < 0.005). Expression levels for IL-18 and the TLRs were increased after 30 minutes of reperfusion. Only IL-18 and TLR-2 were statistically significant (IL-18: p < 0.0001 vs. TLR-2: p < 0.01). The mRNA expression levels for AIF-1 I2 and IL-18 were decreased from the original levels of ischemia after 60 and 90 minutes reperfusion. The TLR-2 and-4 were presented with minimal levels of reduction after 60 minutes. However, mRNA expression levels for all were decreased to the original levels of ischemia after 90 minutes, except for AIF-1 I3, but the difference was not statistically significant. AIF-1 and IL-18 were specifically detected in myocytes and interstitial tissues by immunohistochemistry (IHC) stain after IRI. TLR-4 was non-specific, and TLR2 was minimally expressed. The study discusses the evidence supporting that the AIF-1 may have therapeutic potential for strategies in the control of innate immune responses early on, after transplantation.

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“…Comparing clusters of deregulated genes, we identified AIF-1 as a possible marker gene of rcMACs after overlapping inflammation and unloading transcriptomic results. It is known that AIF-1 is induced by IFN-γ stimulation and plays a role in warm and cold ischemia–reperfusion injury in the rat liver [ 20 ] or is expressed by macrophages in injured skeletal muscles [ 23 ]. We now add to the knowledge that AIF-1 may be involved as a marker of inflammation in the unloaded heart.…”

Section: Discussionmentioning

confidence: 99%

Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model

Waleczek

Sansonetti

et al. 2022

Basic Res Cardiol

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Resident cardiac macrophages (rcMACs) are among the most abundant immune cells in the heart. Plasticity and activation are hallmarks of rcMACs in response to changes in the microenvironment, which is essential for in vitro experimentation. The in vivo investigation is confounded by the infiltration of other cells hindering direct studies of rcMACs. As a tool to investigate rcMACs, we applied the ex vivo model of living myocardial slices (LMS). LMS are ultrathin ex vivo multicellular cardiac preparations in which the circulatory network is interrupted. The absence of infiltration in this model enables the investigation of the rcMACs response to immunomodulatory and mechanical stimulations. Such conditions were generated by applying interferon-gamma (IFN-γ) or interleukine-4 (IL-4) and altering the preload of cultured LMS, respectively. The immunomodulatory stimulation of the LMS induced alterations of the gene expression pattern without affecting tissue contractility. Following 24 h culture, low input RNA sequencing of rcMACs isolated from LMS was used for gene ontology analysis. Reducing the tissue stretch (unloading) of LMS altered the gene ontology clusters of isolated rcMACs with intermediate semantic similarity to IFN-γ triggered reaction. Through the overlap of genes affected by IFN-γ and unloading, we identified Allograft inflammatory factor 1 (AIF-1) as a potential marker gene for inflammation of rcMACs as significantly altered in whole immunomodulated LMS. MicroRNAs associated with the transcriptomic changes of rcMACs in unloaded LMS were identified in silico. Here, we demonstrate the approach of LMS to understand load-triggered cardiac inflammation and, thus, identify potential translationally important therapeutic targets.

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Allograft Inflammatory Factor-1 is Up-regulated in Warm and Cold Ischemia-Reperfusion Injury in Rat Liver and May be Inhibited by FK506

Cited by 11 publications

References 28 publications

Improving the function of liver grafts exposed to warm ischemia by the leuven drug protocol: Exploring the molecular basis by microarray

Improving the function of liver grafts exposed to warm ischemia by the leuven drug protocol: Exploring the molecular basis by microarray

Allograft Inflammatory Factor-1 in Cardiac Ischemia Re-perfusion Injury: Release of Molecular Markers in an <i>in Vitro</i> Setting

Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model

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Allograft Inflammatory Factor-1 is Up-regulated in Warm and Cold Ischemia-Reperfusion Injury in Rat Liver and May be Inhibited by FK506

Cited by 11 publications

References 28 publications

Improving the function of liver grafts exposed to warm ischemia by the leuven drug protocol: Exploring the molecular basis by microarray

Improving the function of liver grafts exposed to warm ischemia by the leuven drug protocol: Exploring the molecular basis by microarray

Allograft Inflammatory Factor-1 in Cardiac Ischemia Re-perfusion Injury: Release of Molecular Markers in an &lt;i&gt;in Vitro&lt;/i&gt; Setting

Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model

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Allograft Inflammatory Factor-1 in Cardiac Ischemia Re-perfusion Injury: Release of Molecular Markers in an <i>in Vitro</i> Setting