scholarly journals Gene Silencing of 4-1BB by RNA Interference Inhibits Acute Rejection in Rats with Liver Transplantation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Yang Shi ◽  
Shuqun Hu ◽  
Qingwei Song ◽  
Shengcai Yu ◽  
Xiaojun Zhou ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Rna Interference ◽  
Acute Rejection ◽  
Gene Silencing ◽  
Signal Pathway ◽  
Brown Norway ◽  
Transplantation Tolerance ◽  
Splenic Lymphocytes ◽  
Liver Morphology

The 4-1BB signal pathway plays a key role in organ transplantation tolerance. In this study, we have investigated the effect of gene silencing of 4-1BB by RNA interference (RNAi) on the acute rejection in rats with liver transplantation. The recombination vector of lentivirus that contains shRNA targeting the 4-1BB gene (LV-sh4-1BB) was constructed. The liver transplantation was performed using the two-cuff technique. Brown-Norway (BN) recipient rats were infected by the recombinant LVs. The results showed that gene silencing of 4-1BB by RNAi downregulated the 4-1BB gene expression of the splenic lymphocytesin vitro, and the splenic lymphocytes isolated from the rats with liver transplantation. LV-sh4-1BB decreased the plasma levels of liver injury markers including AST, ALT, and BIL and also decreased the level of plasma IL-2 and IFN-γin recipient rats with liver transplantation. Lentivirus-mediated delivery of shRNA targeting 4-1BB gene prolonged the survival time of recipient and alleviated the injury of liver morphology in recipient rats with liver transplantation. In conclusion, our results demonstrate that gene silencing of 4-1BB by RNA interference inhibits the acute rejection in rats with liver transplantation.

scholarly journals RNA interference-mediated gene silencing in murine T cells: in vitro and in vivo validation of proinflammatory target genes

2008 ◽  
Vol 6 (1) ◽  
pp. 3 ◽  
Author(s):  
Tatjana C Gust ◽  
Luisa Neubrandt ◽  
Claudia Merz ◽  
Khusru Asadullah ◽  
Ulrich Zügel ◽  
...  
Keyword(s):  
T Cells ◽  
Rna Interference ◽  
Gene Silencing ◽  
Target Genes ◽  
In Vivo Validation

The Role of Tacrolimus Nanomicelles in Acute Rejection After Liver Transplantation in Rats

2021 ◽  
Vol 21 (2) ◽  
pp. 1061-1069
Author(s):  
Zhantao Xie ◽  
Huibo Zhao ◽  
Yuan Chen ◽  
Sidong Wei ◽  
Jianjun Sun ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Liver Transplantation ◽  
Animal Model ◽  
Acute Rejection ◽  
Rat Liver ◽  
Brown Norway ◽  
Rat Liver Transplantation ◽  
Transplantation Model

Although there is some progress in immunosuppressive therapy of acute rejection, there is still a lack of standardized diagnosis and treatment. For the acute rejection after liver transplantation, there is still a lack of an exact treatment at this stage. Tacrolimus (TAC) side effects will also affect the survival rate and quality of life of recipients after transplantation to a large extent. Rat orthotopic liver transplantation model was established and divided into three groups. In the tolerance group, Brown Norway (BN) to Lewis liver transplantation was used; in the rejection group, Lewis to BN liver transplantation was used; in the TAC group, TAC was injected after operation on the basis of establishing rejection model. The expression of GITRL in Kupffer cells and the change of cytokines were detected 7 days after operation. In this study, the animal model of acute rejection of rat liver transplantation was established to simulate the clinical allogeneic liver transplantation, and the important role of TAC in the acute rejection of rat liver transplantation was evaluated.

Gene silencing in adult rat cardiac myocytes in vitro by adenovirus-mediated RNA interference

2006 ◽  
Vol 27 (5-7) ◽  
pp. 413-421 ◽  
Author(s):  
Andreas Rinne ◽  
Christoph Littwitz ◽  
Marie-Cécile Kienitz ◽  
Andreas Gmerek ◽  
Leif I. Bösche ◽  
...  
Keyword(s):  
Rna Interference ◽  
Gene Silencing ◽  
Cardiac Myocytes ◽  
Adult Rat ◽  
Rat Cardiac Myocytes

scholarly journals HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huan Cao ◽  
Longlong Wu ◽  
Xuan Tian ◽  
Weiping Zheng ◽  
Mengshu Yuan ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Acute Rejection ◽  
T Cell Activation ◽  
Heme Oxygenase 1 ◽  
Machine Perfusion ◽  
Inhibitory Receptors ◽  
Donor Liver ◽  
Nkt Cell ◽  
Normothermic Machine Perfusion

Abstract Background Liver transplantation (LT) is required in many end-stage liver diseases. Donation after cardiac death (DCD) livers are often used, and treatment of acute rejection (ACR) requires the use of immunosuppressive drugs that are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in treatment following LT; however, they have limitations, including low colonization in the liver. An optimized BMMSC application method is required to suppress ACR. Methods BMMSCs were isolated and modified with the heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT into rats. The severity of ACR was evaluated based on liver histopathology. Gene chip technology was used to detect differential gene expression, and flow cytometry to analyze changes in natural killer (NK) T cells. Results NMP induced BMMSCs to colonize the donor liver during in vitro preservation. The survival of HO-1/BMMSCs in liver grafts was significantly longer than that of unmodified BMMSCs. When the donor liver contained HO-1/BMMSCs, the local immunosuppressive effect was improved and prolonged, ACR was controlled, and survival time was significantly prolonged. The application of HO-1/BMMSCs reduced the number of NKT cells in liver grafts, increased the expression of NKT cell co-inhibitory receptors, and reduced NKT cell expression of interferon-γ. Conclusions NK cell and CD8+ T cell activation was inhibited by application of HO-1/BMMSCs, which reduced ACR of transplanted liver. This approach could be developed to enhance the success rate of LT.

scholarly journals Which Incision is Better for Orthotopic Rat Liver Transplantation, Transverse or Midline?

2021 ◽  
Author(s):  
Gaofeng Tang ◽  
Zhongwu Zou ◽  
Huibo Zhao ◽  
Weiwei Wang ◽  
Guoyong Chen ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Survival Rate ◽  
Acute Rejection ◽  
Rat Liver ◽  
Brown Norway ◽  
Control Group ◽  
Sprague Dawley ◽  
Transverse Incision ◽  
Rat Liver Transplantation ◽  
Biting Behavior

Abstract Orthotopic rat liver transplantation (OLT) is a complex procedure extensively applicable to basic science, myriad complications can occur, incision-related self-biting has not been reported after liver transplantation. For the project of tolerance induction through stem cells, OLT was performed from inbred Sprague Dawley (SD) rat to SD (control group, n = 9), SD to Lewis (chronic rejection, n = 11), and OLT from Lewis allograft to Brown Norway (BN) rats (acute rejection, n = 63), the acute rejection group was sub-grouped into the transverse incision group(n = 26) and midline group(n = 37), Cyclosporine A was injected at 2mg/kg into the rejection groups once daily for 14 days, lidocaine cream alone or with naloxone was used for pain-relieving. The recipient survival and wound status were the primary endpoint of this study. For SD→SD, 30-day survival rate was 88.9%, no self-biting behavior occurred; for SD→Lewis, 30-day survival rate was 54.5%, the degree II of self-biting occurred in 2 cases. For Lewis→BN with transverse incision, 30-day survival rate was 51.8%, severe self-biting occurred in 16 cases in 8–27 days and 5 more cases over 30 days, which caused death or euthanasia, the degree 2 of biting occurred in 2 cases. For Lewis→BN with midline incision, 30-day survival rate was 86.0%, no severe self-biting occurred, mild self-biting in 2 cases. There was difference in the biting–related survival between two sub-groups (p = 0.003). In conclusion, incision-related self-biting behavior is species-specific for rats, the transverse incision is the pain-causing reason; the midline one is effective to avert occurrences.

scholarly journals Induction of Donor-Specific Transplantation Tolerance to Skin and Cardiac Allografts Using Mixed Chimerism in (A + B → A) in Rats

1993 ◽  
Vol 2 (4) ◽  
pp. 345-353 ◽  
Author(s):  
Peter M. Markus ◽  
Gennaro Selvaggi ◽  
Xin Cai ◽  
John J. Fung ◽  
Thomas E. Starzl
Keyword(s):  
Lymphoid Cells ◽  
Third Party ◽  
Mixed Chimerism ◽  
Brown Norway ◽  
Transplantation Tolerance ◽  
Solid Organ ◽  
Relative Ease ◽  
Histocompatibility Complex ◽  
Cardiac Allografts

Mixed allogeneic chimerism (A + B → A) was induced in rats by reconstitution of lethally irradiated LEW recipients with a mixture of T-cell depleted (TCD) syngeneic and TCD allogeneic ACI bone marrow. Thirty-seven percent of animals repopulated as stable mixed lymphopoietic chimeras, while the remainder had no detectable allogeneic chimerism. When evaluated for evidence of donor-specific transplantation tolerance, only those recipients with detectable allogeneic lymphoid chimerism exhibited acceptance of donor-specific skin and cardiac allografts. Despite transplantation over a major histocompatibility complex (MHC)- and minor-disparate barrier, animals accepted donor-specific ACI skin and primarily vascularized cardiac allografts permanently, while rejecting third party Brown Norway (BN) grafts. The tolerance induced was also donor-specific in vitro as evidenced by specific hyporeactivity to the allogeneic donor lymphoid elements, yet normal reactivity to MHC-disparate third party rat lymphoid cells. This model for mixed chimerism in the rat will be advantageous to investigate specific transplantation tolerance to primarily vascularized solid organ grafts that can be performed with relative ease in the rat, but not in the mouse, and may provide a method to study the potential existence of organ- or tissue-specific alloantigens in primarily vascularized solid organ allografts.

RNA interference in plant parasitic nematodes: a summary of the current status

Parasitology ◽  
2012 ◽  
Vol 139 (5) ◽  
pp. 630-640 ◽  
Author(s):  
C. J. LILLEY ◽  
L. J. DAVIES ◽  
P. E. URWIN
Keyword(s):  
Rna Interference ◽  
Gene Silencing ◽  
Cell Types ◽  
Current Status ◽  
Parasitic Nematodes ◽  
Rnai Phenotype ◽  
Plant Parasitic Nematodes ◽  
Systemic Rnai ◽  
Plant Parasitic

SUMMARYRNA interference (RNAi) has emerged as an invaluable gene-silencing tool for functional analysis in a wide variety of organisms, particularly the free-living model nematode Caenorhabditis elegans. An increasing number of studies have now described its application to plant parasitic nematodes. Genes expressed in a range of cell types are silenced when nematodes take up double stranded RNA (dsRNA) or short interfering RNAs (siRNAs) that elicit a systemic RNAi response. Despite many successful reports, there is still poor understanding of the range of factors that influence optimal gene silencing. Recent in vitro studies have highlighted significant variations in the RNAi phenotype that can occur with different dsRNA concentrations, construct size and duration of soaking. Discrepancies in methodology thwart efforts to reliably compare the efficacy of RNAi between different nematodes or target tissues. Nevertheless, RNAi has become an established experimental tool for plant parasitic nematodes and also offers the prospect of being developed into a novel control strategy when delivered from transgenic plants.

scholarly journals HO-1/Bmmscs Perfusion Using a Normothermic Machine Perfusion System Reduces the Acute Rejection of DCD Liver Transplantation by Regulating NKT Cell Co-Inhibitory Receptors

2021 ◽  
Author(s):  
Huan Cao ◽  
Longlong Wu ◽  
Xuan Tian ◽  
Weiping Zheng ◽  
Mengshu Yuan ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Acute Rejection ◽  
Survival Time ◽  
Nkt Cells ◽  
Machine Perfusion ◽  
Donor Liver ◽  
Nkt Cell ◽  
Normothermic Machine Perfusion ◽  
Ifn Γ

Abstract Background: Liver transplantation (LT) represents the most effective treatment for many end-stage liver diseases. While donation after cardiac death (DCD) donor livers are used due to organ shortage, acute rejection (ACR) remains an important risk factor affecting the survival of recipients following transplantation. Although immunosuppressive agents can be used, they are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in the treatment of organ transplantation; however, there is limited colonization in the target organs and a short survival time following BMMSCs application. Thus, an optimized BMMSCs application method is required to suppress immune rejection and promote the long-term survival of allogeneic liver transplant recipients. Methods: BMMSCs were isolated and modified with heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into the donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT. The severity of ACR was evaluated based on the liver histopathology. Gene chip technology was used to detect differential gene expression, and the flow cytometry was used to analyze changes in natural killer (NK) T cells. Results: NMP can induce BMMSCs to colonize the donor liver during in vitro preservation, and the survival of HO-1/BMMSCs in the liver grafts was significantly longer than that of BMMSCs. When the donor liver contained HO-1/BMMSCs, the ACR is obviously controlled, and the survival time was significantly prolonged. The application of HO-1/BMMSCs reduces the number of NKT cells in the liver grafts, increases the expression of the NKT cell co-inhibitory receptors, and reduces the level of NKT cell expression of IFN-γ. Thus, NK cell and CD8+ T cell activation was inhibited, which reduced acute of rejection of the transplanted liver. Conclusions: The NMP system preserves the DCD donor liver in vitro, and also allows large quantities of BMMSCs to colonize the liver. HO-1-modified BMMSCs are able to improve and prolong the local immunosuppressive effect of BMMSCs following transplantation by reducing the number of NKT cells and up-regulating NKT cell co-inhibitory receptor expression. This results in the transmission of inhibitory signals to NKT cells, reduced NKT cell IFN-γ levels, and the inhibition of ACR.

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