The interleukin-6/interleukin-6-receptorsystem is activated in donor hearts

Plenz, Gabriele; Eschert, Heike; Erren, Michael; Wichter, Thomas; Böhm, Michael; Flesch, Markus; Scheld, Hans H.; Deng, Mario C.

doi:10.1016/s0735-1097(02)01791-6

Cited by 83 publications

(66 citation statements)

References 35 publications

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“…IL-6 is a proinflammatory cytokine that has numerous effects on T cell activation, differentiation, and recruitment (66)(67)(68). In the context of transplantation, increased levels of IL-6 correlated with adverse outcomes in human allograft recipients (69,70). IL-6 is known to inhibit the function of natural Tregs (71), as well as the induction of iTregs (52).…”

Section: Discussionmentioning

confidence: 99%

Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells

Wang¹,

Yi²,

Qin³

et al. 2013

J. Clin. Invest.

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Human graft endothelial cells (ECs) can act as antigen-presenting cells to initiate allograft rejection by host memory T cells. Rapamycin, an mTOR inhibitor used clinically to suppress T cell responses, also acts on DCs, rendering them tolerogenic. Here, we report the effects of rapamycin on EC alloimmunogenicity. Compared with mock-treated cells, rapamycin-pretreated human ECs (rapa-ECs) stimulated less proliferation and cytokine secretion from allogeneic CD4 + memory cells, an effect mimicked by shRNA knockdown of mTOR or raptor in ECs. The effects of rapamycin persisted for several days and were linked to upregulation of the inhibitory molecules PD-L1 and PD-L2 on rapa-ECs. Additionally, rapa-ECs produced lower levels of the inflammatory cytokine IL-6. CD4 + memory cells activated by allogeneic rapa-ECs became hyporesponsive to restimulation in an alloantigen-specific manner and contained higher percentages of suppressive CD4 + CD25 hi CD127 lo FoxP3 + cells that did not produce effector cytokines. In a human-mouse chimeric model of allograft rejection, rapamycin pretreatment of human arterial allografts increased graft EC expression of PD-L1 and PD-L2 and reduced subsequent infiltration of allogeneic effector T cells into the artery intima and intimal expansion. Preoperative conditioning of allograft ECs with rapamycin could potentially reduce immune-mediated rejection.

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Section: Discussionmentioning

confidence: 99%

Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells

Wang¹,

Yi²,

Qin³

et al. 2013

J. Clin. Invest.

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“…This understanding can lead to the explanation of association between elevated serum IL6 concentrations and acute cardiac allograft dysfunction in the early postoperative period. 53) Myocardial and serum IL-6 levels from donors with myocardial dysfunction (unused donors), from donors with good ventricular function (used donors), and from patients with advanced heart failure were examined. Increased expression of IL-6 in the myocardium of all donor hearts showing marked dysfunction was found.…”

Section: )mentioning

confidence: 99%

Interleukin-6 and Cardiovascular Diseases

2004

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SUMMARYInflammatory cytokines are important for both cardiovascular scientists and practicing clinicians. Interleukin-6 (IL-6) has been emphasized by reports of elevated circulating as well as intracardiac IL-6 levels in patients with congestive heart failure (CHF). IL-6 may contribute to the progression of myocardial damage and dysfunction in chronic heart failure syndrome resulting from different causes. As the cause of CHF in cardiomyopathy, myocarditis, allograft rejection, and left ventricular assist device (LVADs) conditions, circulating IL-6 levels are associated with the severity of left ventricular dysfunction, and are also strong predictors of subsequent clinical outcomes. Continuous and excessive production of IL-6 promotes myocardial injury by breaking down both cytokine networks and viral clearance under viral myocarditis. Although IL-6 is likely important in the process of viral antigen presentation, early activation of immune responses and attenuation of viral replication also appear to be significant in an animal model of viral myocarditis. IL-6 can cause cardiac hypertrophy through the IL-6 signal transducing receptor component, glycoprotein 130. There are several interesting cases of cardiac myxoma complicated with mediastinal lymphadenopathy or left ventricular hypertrophy. Increased expression of IL-6 is observed in the myocardium of all donor hearts showing marked dysfunction. Myocardial IL-6 concentrations are also significantly higher in LVAD candidates compared with advanced heart failure patients. Although the IL-6 family plays a central role in the pathophysiology of cardiovascular diseases, it remains to be determined whether the IL-6 family is beneficial or detrimental. Future study will be needed to resolve this question. (Jpn Heart J 2004; 45: 183-193)

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“…IL6 is significantly associated with breast cancer (Hefler et al, 2005), lung cancer (Noponen-Hietala et al, 2005), intervertebral disc disease (NoponenHietala et al, 2005), and neuroblastoma (Egler et al, 2008). The expression of IL6 receptor components in the myocardium of donor hearts before transplantation was investigated by Plenz et al (2002).…”

Section: Discussionmentioning

confidence: 99%

Protein-protein interaction network and mechanism analysis of hepatitis C

Tang¹,

Tang²,

Dong³

et al. 2015

Genet. Mol. Res.

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ABSTRACT.We predicted potential genes and identified pathways associated with hepatitis C. The gene expression profiles of GSE40184 from blood samples and GSE38597 from liver biopsy samples were downloaded from the GEO database. Differentially expressed genes (DEGs) were recognized using the Limma Package. The Pearson correlation test was used to construct the co-expression network of DEGs. Gene set enrichment analysis was used to define significant functions and pathways for DEGs. A total of 165 DEGs in blood samples and 523 DEGs in liver biopsy samples were identified. Eight DEGs were common between these samples. Gene Ontology enrichment analysis showed that 165 DEGs in blood samples were significantly enriched regarding the response to protein binding, receptor binding, G-protein coupled receptor binding, cytokine receptor binding, and cytokine activity. The most significant term of the Kyoto Encyclopedia of Genes and Genomes pathway was the cytokine-cytokine receptor (2015) interaction. Protein-protein interaction network analysis indicated that three subnetworks with more nodes and edges were involved in these interactions. We used robust biomarkers that were differentially expressed in hepatitis C and determined their relevance in the biological function, signal pathways, protein-protein interaction network, and coexpression network of hepatitis C.

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The interleukin-6/interleukin-6-receptorsystem is activated in donor hearts

Cited by 83 publications

References 35 publications

Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells

Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells

Interleukin-6 and Cardiovascular Diseases

Protein-protein interaction network and mechanism analysis of hepatitis C

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