scholarly journals Tumor necrosis factor-α gene polymorphism is associated with short- and long-term kidney allograft outcomes.

2021 ◽  
Author(s):  
Felix Poppelaars ◽  
Mariana Gaya da Costa ◽  
Bernardo Faria ◽  
Siawosh K. Eskandari ◽  
Marc A. Seelen ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Tumor Necrosis Factor ◽  
Graft Survival ◽  
Tumor Necrosis ◽  
Graft Loss ◽  
Tnf Alpha ◽  
Kidney Graft ◽  
Genotype Group ◽  
Necrosis Factor

Introduction Kidney transplantation has excellent short-term results with current immunosuppression regimes, but long-term outcomes have barely improved. Hence, there is a need for new therapeutic options to increase long-term survival of kidney grafts. Drug development for transplantation has slowly plateaued, limiting progress while making drug repurposing an attractive alternative. We, therefore, investigated the impact of tumor necrosis factor-alpha (TNF-alpha) gene (TNF) polymorphisms on kidney graft survival. Methods We performed a prospective cohort study to assess the association of TNF polymorphisms (rs1800629 G>A and rs3093662 A>G) with primary non-function (PNF) and death-censored kidney allograft survival in 1,271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands. Results The G-allele of the TNF rs3093662 polymorphism in donor kidneys was associated with a higher risk of PNF (odds ratio: 2.05; 95%-CI: 1.06-3.97; P = 0.032). Furthermore, the G-allele of this TNF rs3093662 polymorphism in the donor was also associated with worse 5-year, 10-year, and 15-year death-censored kidney graft survival (P<0.05). The cumulative incidence of graft loss was 15.9% in the reference AA-genotype group and 25.2% in the AG/GG-genotype group, respectively. In multivariable analysis, the association between the TNF rs3093662 polymorphism in the donor and 15-year death-censored kidney graft survival remained significant (hazard ratio: 1.51; 95%-CI: 1.05-2.19, P = 0.028). Conclusion Kidney allografts possessing a high-producing TNF polymorphism have a greater risk of immediate and late graft loss. Our study adds to a growing body of literature indicating the potential of TNF-alpha blockade in improving kidney transplantation outcomes.

scholarly journals A functional TGFB1 polymorphism in the donor associates with long-term graft survival after kidney transplantation.

2021 ◽  
Author(s):  
Felix Poppelaars ◽  
Mariana Gaya da Costa ◽  
Bernardo Faria ◽  
Siawosh K. Eskandari ◽  
Jeffrey Damman ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Loss ◽  
Kidney Graft ◽  
Genotype Group ◽  
Transplant Survival ◽  
Increased Risk ◽  
The Impact

Introduction Improvement of long-term outcomes in kidney transplantation remains one of the most pressing challenges, yet drug development is stagnating. Human genetics offers an opportunity for much-needed target validation in transplantation. Conflicting data exists about the effect of transforming growth factor beta 1 (TGF-beta1) on kidney transplant survival, since TGF-beta1 has profibrotic and protective effects. We therefore the impact of a recently discovered functional TGBF1 polymorphism on long term kidney graft survival. Methods We performed an observational cohort study analyzing recipient and donor DNA in 1,271-kidney transplant pairs from the University Medical Center Groningen in The Netherlands and associated a low-producing TGBF1 polymorphism (rs1800472 C>T) with 5, 10, and 15-year death-censored kidney graft survival. Results Donor genotype frequencies of s1800472 in TGBF1 differed significantly between patients with and without graft loss (P=0.042). Additionally, the low-producing TGBF1 polymorphism in the donor was associated with an increased risk of graft loss following kidney transplantation (HR 2.13 for the T allele; 95%-CI 1.16-3.90; P=0.015). The incidence of graft loss within 15 years of follow-up was 16.4% in the CC-genotype group and 28.9% in the CT-genotype group. After adjustment for transplant-related covariates, the association between the TGBF1 polymorphism in the donor and graft loss remained significant. In contrast, there was no association between the TGBF1 polymorphism in the recipient and graft loss. Conclusion Kidney allografts possessing a low-producing TGBF1 polymorphism have a higher risk of late graft loss. Our study adds to a growing body of evidence that TGFbeta1 is beneficial, rather than harmful, for kidney transplant survival.

scholarly journals Tumor necrosis factor (TNF)-induced protein phosphorylation in a human rhabdomyosarcoma cell line is mediated by 60-kD TNF receptors (TR60)

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2211-2220 ◽  
Author(s):  
A Mire-Sluis ◽  
A Meager
Keyword(s):  
Tumor Necrosis Factor ◽  
Protein Phosphorylation ◽  
Cell Line ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Tnf Receptors ◽  
Protein Kinase C Inhibitors ◽  
Rhabdomyosarcoma Cell Line ◽  
Rhabdomyosarcoma Cell ◽  
Necrosis Factor

Abstract In the present study, we used a cloned derivative, KYM-1D4, of the human rhabdomyosarcoma cell line, KYM-1, known to express high numbers of the two tumor necrosis factor (TNF) receptors, TR60 and TR80, and to be highly sensitive to TNF alpha-mediated cytotoxicity/antiproliferation, to investigate the role of TR60 and TR80 in protein phosphorylation. Using permeabilized KYM-1D4 cells, it was found that TNF alpha strongly induced phosphorylation of proteins of molecular weight 80, 65, 58, 42, and 30 kD. Addition of a monoclonal antibody (MoAb) against TR60 was shown to induce cytotoxicity/antiproliferation in KYM-1D4 cells and the same pattern of protein phosphorylation as TNF alpha, whereas addition of an MoAb against TR80 was both noncytotoxic and ineffective in inducing protein phosphorylation. In contrast, in a highly TNF alpha-resistant KYM-1- derived cell line, 37B8R, no protein phosphorylation was induced with either TNF alpha or the agonistic anti-TR60 MoAb. However, when 37B8R was allowed to revert to partial TNF sensitivity by culture in the absence of TNF alpha, the resultant cell line, 37B8S, was found to regain inducibility of protein phosphorylation by TNF alpha. These results indicate that expression of functional TR60 in KYM-1-related cell lines is principally involved in TNF-mediated cytotoxicity/antiproliferation and is necessary for the induction of protein phosphorylation. Nevertheless, the latter, although apparently strongly associated with cytotoxicity, was probably involved in protective mechanisms because protein kinase C inhibitors that inhibited TNF alpha and anti-TR60-induced phosphorylation increased the cytotoxic/antiproliferative response to these mediators.

scholarly journals Impact of Early Pancreatic Graft Loss on Outcome after Simultaneous Pancreas–Kidney Transplantation (SPKT)—A Landmark Analysis

2021 ◽  
Vol 10 (15) ◽  
pp. 3237
Author(s):  
Lukas Johannes Lehner ◽  
Robert Öllinger ◽  
Brigitta Globke ◽  
Marcel G. Naik ◽  
Klemens Budde ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Graft Loss ◽  
Type I ◽  
Kidney Graft ◽  
Landmark Analysis ◽  
Pancreas Kidney Transplantation ◽  
Simultaneous Pancreas Kidney ◽  
Simultaneous Pancreas Kidney Transplantation ◽  
Pancreas Graft

(1) Background: Simultaneous pancreas–kidney transplantation (SPKT) is a standard therapeutic option for patients with diabetes mellitus type I and kidney failure. Early pancreas allograft failure is a complication potentially associated with worse outcomes. (2) Methods: We performed a landmark analysis to assess the impact of early pancreas graft loss within 3 months on mortality and kidney graft survival over 10 years. This retrospective single-center study included 114 adult patients who underwent an SPKT between 2005 and 2018. (3) Results: Pancreas graft survival rate was 85.1% at 3 months. The main causes of early pancreas graft loss were thrombosis (6.1%), necrosis (2.6%), and pancreatitis (2.6%). Early pancreas graft loss was not associated with reduced patient survival (p = 0.168) or major adverse cerebral or cardiovascular events over 10 years (p = 0.741) compared to patients with functioning pancreas, after 3 months. Moreover, kidney graft function (p = 0.494) and survival (p = 0.461) were not significantly influenced by early pancreas graft loss. (4) Conclusion: In this study, using the landmark analysis technique, early pancreas graft loss within 3 months did not significantly impact patient or kidney graft survival over 10 years.

Tumor necrosis factor-alpha inhibits lipid and lipoprotein transport by Caco-2 cells

1995 ◽  
Vol 269 (6) ◽  
pp. G953-G960 ◽  
Author(s):  
M. Mehran ◽  
E. Seidman ◽  
R. Marchand ◽  
C. Gurbindo ◽  
E. Levy
Keyword(s):  
Lipid Metabolism ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Low Density Lipoproteins ◽  
Tnf Alpha ◽  
Low Density ◽  
Necrosis Factor Alpha ◽  
Apo B ◽  
Factor Alpha ◽  
Necrosis Factor

Cytokines, important mediators of inflammation, have been shown to cause disturbances in circulating and hepatic lipid metabolism. Although the intestine plays a major role in dietary fat transport and largely contributes to plasma lipoproteins, the effects of cytokines on intestinal lipid handling remain unknown. In the present study, the modulation of lipid, apoprotein, and lipoprotein synthesis and secretion by tumor necrosis factor-alpha (TNF-alpha) was investigated in Caco-2 cells. Highly differentiated and polarized cells (20 days in culture) were incubated for 20 h with recombinant human TNF-alpha (100-500 ng/ml). No cytotoxic effect of TNF-alpha cells was observed, as indicated by the determinations of Caco-2 cell viability and monolayer transepithelial resistance. Moreover, no differences in cell maturation (sucrase activity) or cell proliferation ([3H]thymidine incorporation and cell cycle analysis) were detected between treated and control cultures. Significant inhibition of lipid secretion by TNF-alpha was observed, with the greatest reduction at 500 ng/ml. TNF-alpha significantly decreased Caco-2 cell secretion of phospholipids (22%), triglycerides (30%), and cholesteryl ester (37%). It also significantly diminished the export of newly synthesized low-density lipoproteins (LDL; 20%) and high-density lipoproteins (HDL; 13%), with a lesser effect on very low-density lipoproteins (VLDL; 3%). The lipid composition of these lipoproteins was minimally affected. De novo synthesis of apo A-I, apo B-100, and apo B-48 was also markedly reduced by TNF-alpha. Sphingomyelinase activity was not increased and cell content of sphingomyelin was not altered, suggesting that inhibitory effects on lipid and apoprotein of TNF-alpha were not mediated by the ceramide pathway. Our results indicate that TNF-alpha may play a role in modulating intestinal lipid metabolism, thus affecting circulating lipoproteins.

ROLE OF INTER LEUKIN 10 AND TUMOR NECROSIS FACTOR-ΑLPHA IN PANCREATITIS

2021 ◽  
pp. 14-17
Author(s):  
Mukherjee.J. R ◽  
Mukherjee. B ◽  
Roy. S ◽  
Jana. D ◽  
Bandopadhyay. S ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
General Surgery ◽  
Tumor Necrosis ◽  
Cell Injury ◽  
Gall Stone ◽  
Tnf Alpha ◽  
Tnf Α ◽  
The Mean ◽  
Necrosis Factor

Background: Pancreatic acinar cell injury triggers the synthesis and release of pro-inammatory cytokines and chemokines. The involvement of several pro-inammatory and anti-inammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-33 and tumor necrosis factor-α is involved in the pathogenesis of pancreatitis. Aim: This study aims to validate the role of activation of TNF-alpha and IL-10 as a biomaker marker in patients with Pancreatitis in Indian subcontinent.Material and methods: 50 Patients of Pancreatitis attending general surgery OPD and admitted to General Surgery department of SSKM Hospital, Kolkata, West Bengal, India were taken. Result: It was found that in alcoholic, the mean TNF - α (mean±s.d.) of the patients was 19.4027 ± 8.3275 pg/ml. In ascites, the mean TNF - α (mean±s.d.) of the patients was 19.9767 ± 2804 pg/ml. In chronic, the mean TNF - α (mean±s.d.) of the patients was 18.8533 ± 8.4674 pg/ml. In gall stone, the mean TNF - α (mean±s.d.) of the patients was 16.3421 ± 9.9499 pg/ml. In osteoarthritis, the mean TNF - α (mean±s.d.) of the patients was 12.4750 ± 8.3085 pg/ml. Distribution of mean TNF - α vs. association was not statistically signicant (p=0.7309).Conclusion: It was found that IL10 was higher in Ascites patients though it was not statistically signicant. TNF alpha was higher in Ascites patients. TNF alpha was higher in normal Pancreatitis.

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