scholarly journals Critical role of the calpain/calpastatin balance in acute allograft rejection

2010 ◽  
Vol 41 (2) ◽  
pp. 473-484 ◽  
Author(s):  
Emmanuel Letavernier ◽  
Boris Dansou ◽  
Matthias Lochner ◽  
Joëlle Perez ◽  
Agnès Bellocq ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Critical Role ◽  
Acute Allograft Rejection

scholarly journals Critical role of the Toll-like receptor signal adaptor protein MyD88 in acute allograft rejection

2003 ◽  
Vol 111 (10) ◽  
pp. 1571-1578 ◽  
Author(s):  
Daniel R. Goldstein ◽  
Bethany M. Tesar ◽  
Shizuo Akira ◽  
Fadi G. Lakkis
Keyword(s):  
Allograft Rejection ◽  
Critical Role ◽  
Adaptor Protein ◽  
Toll Like Receptor ◽  
Acute Allograft Rejection ◽  
Receptor Signal

The Critical Role of Induced CD4+ FoxP3+ Regulatory Cells in Suppression of Interleukin-17 Production and Attenuation of Mouse Orthotopic Lung Allograft Rejection

2015 ◽  
Vol 99 (7) ◽  
pp. 1356-1364 ◽  
Author(s):  
Wenyong Zhou ◽  
Xiaohui Zhou ◽  
Saren Gaowa ◽  
Qingshu Meng ◽  
Zhenzhen Zhan ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Critical Role ◽  
Interleukin 17 ◽  
Regulatory Cells

Critical Role of Proinflammatory Cytokine IL-6 in Allograft Rejection and Tolerance

2011 ◽  
Vol 12 (1) ◽  
pp. 90-101 ◽  
Author(s):  
X. Zhao ◽  
O. Boenisch ◽  
M. Yeung ◽  
B. Mfarrej ◽  
Sunmi Yang ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Proinflammatory Cytokine ◽  
Critical Role

Abstract 3689: Loss of Myeloid Related Protein-8/14 Exacerbates Cardiac Allograft Rejection

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Koichi Shimizu ◽  
Peter Libby ◽  
Viviane Z Rocha ◽  
Eduardo J Folco ◽  
Rica Shubiki ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Antigen Presentation ◽  
Allograft Rejection ◽  
Cardiac Transplantation ◽  
Cardiac Allograft ◽  
Mrna Levels ◽  
Acute Allograft Rejection ◽  
Cardiac Allograft Rejection ◽  
Ifn Γ

Background: The S100 calcium-binding proteins MRP-8 (S100A8) and MRP-14 (S100A9) heterodimerize to form MRP-8/14 complexes that regulate myeloid cell function, control inflammatory responses, and serve as an early serum marker for monitoring acute allograft rejection. Despite functioning as a putative pro-inflammatory mediator, the pathophysiological role of MRP-8/14 in cardiovascular disease remains unknown. This study used murine cardiac transplantation to investigate the role of MRP-14 in cardiac allograft rejection using MRP-14-deficient mice (MRP14−/−) lacking MRP-8/14 complexes. Results: In major histocompatibility complex class II allomismatched cardiac transplantation (bm12 donor hearts and C57BL/6 recipients), allograft survival averaged 5.9 ± 2.9 weeks (n=10) in MRP14−/ −recipients compared to > 12 weeks (n = 15, p<0.0001) in wild-type (WT) recipients. At 2 week post-transplantation, allografts in MRP14−/ − recipients had significantly higher parenchymal rejection (PR) scores (2.8 ± 0.8, n=8) than WT recipients (0.8 ± 0.8, n=12, p<0.0001). MRP14−/ − recipients had significantly increased allograft accumulation of T cells and macrophages and mRNA levels of IFN-γ and IFN-γ–associated chemokines (IP-10, Mig, and I-TAC) compared to WT recipients. The MRP14−/− recipients also had significantly more lymphocytes in draining lymph nodes than WT recipients (cell number per lymph nodes: 23.7 ± 0.7 x 105 for MRP14−/− vs. 6.0 ± 0.2 x 105 for WT, p < 0.0001). MRP14−/− dendritic cells (DC) stimulated with IFN-γ expressed significantly higher levels of the co-stimulatory molecules CD86 and ICOSL, and mixed leukocyte reaction using allo-EC-primed MRP14−/− DC resulted in significantly higher antigen-presenting function than WT DC. Conclusion: Taken together, these observations indicate that MRP-8/14 complexes participate in acute allograft rejection by modulating dendritic cell antigen presentation and T cell priming. The unexpected finding that deficiency of MRP-8/14 complexes exacerbates acute allograft rejection indicates that MRP-8/14 has distinct roles in modulating immune cell functions, such as migration and antigen presentation. This research has received full or partial funding support from the American Heart Association, AHA National Center.

scholarly journals A critical role of TRAIL expressed on cotransplanted hepatic stellate cells in prevention of islet allograft rejection

Microsurgery ◽  
2009 ◽  
Vol 30 (4) ◽  
pp. 332-337 ◽  
Author(s):  
Horng-Ren Yang ◽  
Ching-Chuan Hsieh ◽  
Lianfu Wang ◽  
John J. Fung ◽  
Lina Lu ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Allograft Rejection ◽  
Critical Role ◽  
Stellate Cells ◽  
Islet Allograft

Abstract 34: Statins Directly Activate Erk5 and Reduce Endothelial Dysfunction and Acute Allograft Rejection

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Yuichiro Takei ◽  
Nhat-Tu Le ◽  
Hakjoo Lee ◽  
Kyung-Sun Heo ◽  
Cheryl Hurley ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
High Throughput Screening ◽  
Transcriptional Activity ◽  
Vascular Reactivity ◽  
Pleiotropic Effects ◽  
Protective Effects ◽  
Acute Allograft Rejection

Rationale: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are principal therapeutic agents for the treatment of hypercholesteremia. Statins, however, appear to also exert cholesterol-independent pleiotropic effects, such as improvement of endothelial (EC) function, stabilization of fibrous plaques, and decrease vascular inflammation. It is now well established that statins are beneficial in the prevention of cardiovascular disease and also widely used for suppressing cardiac allograft rejection. Previously, we have reported anti-inflammatory effect of ERK5 kinase in ECs. Methods and Results: In this study, we screened small molecules that activate ERK5 using high throughput screening, and identified statins as strong activators of the transcriptional activity of ERK5. In particular, we have found that pitavastatin increases ERK5 transcriptional activity, KLF2 promoter activity, and eNOS mRNA expression in ECs. These effects are abolished by the depletion of ERK5, but not its direct upstream kinase, MEK5. In addition, pitavastatin directly and dose-dependently activates ERK5 kinase activity in an in vitro kinase reaction assay, suggesting that ERK5 is a direct target of this statin. To examine the functional role of EC ERK5 activation by the statin in vivo, we utilized inducible endothelial ERK5 knock out (EC-ERK5-KO) mice and evaluated the effect of pitavastatin on EC function and acute allograft rejection. Depletion of ERK5 in ECs resulted in significant EC inflammation and dysfunction in vivo. Although pitavastatin reduced leukocyte rolling and vascular reactivity in mesebteruc microvessels of diabetic mice and prolonged allograft survival in a full allomismatch combination model, these protective effects were lost in EC-ERK5-KO mice. Conclusion: These data suggest the crucial role of ERK5 in pleiotropic effects of statins on EC dysfunction and allograft rejection in vivo.

scholarly journals Critical Role of Donor Tissue Expression of Programmed Death Ligand-1 in Regulating Cardiac Allograft Rejection and Vasculopathy

Circulation ◽  
2008 ◽  
Vol 117 (5) ◽  
pp. 660-669 ◽  
Author(s):  
Jun Yang ◽  
Joyce Popoola ◽  
Shakila Khandwala ◽  
Nidyanandh Vadivel ◽  
Vijay Vanguri ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Critical Role ◽  
Tissue Expression ◽  
Cardiac Allograft ◽  
Programmed Death Ligand 1 ◽  
Cardiac Allograft Rejection ◽  
Donor Tissue ◽  
Programmed Death
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