Acute allograft rejection in human liver transplant recipients is associated with signaling through toll‐like receptor 4

Testro, Adam; Visvanathan, Kumar; Skinner, Narelle; Markovska, V.; Crowley, Peter; Angus, Peter W; Gow, Paul J

doi:10.1111/j.1440-1746.2010.06324.x

Cited by 42 publications

(35 citation statements)

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“…Because TLR4 has been correlated with various types of acute transplantation rejection131415, we first examined TLR4 expression in the allografted mice. Quantitative analysis using a quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that TLR4 and MyD88 (the critical signaling transducer) expression had been concomitantly up-regulated in the femoral extracts of the allografted mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Growing evidence indicates that TLRs are associated with acute allograft rejection. For example, in liver transplant patients, recipients with acute allograft rejection had higher TLR2 and TLR4 expression levels than did recipients with stable transplants and normal liver function1314. Increased TLR4 expression was also correlated with endothelial dysfunction in cardiac transplant recipients15.…”

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confidence: 99%

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Knockdown of toll-like receptor 4 signaling pathways ameliorate bone graft rejection in a mouse model of allograft transplantation

Hsieh

Shen

et al. 2017

Sci Rep

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Non-union occurring in structural bone grafting is a major problem in allograft transplantation because of impaired interaction between the host and graft tissue. Activated toll-like receptor (TLR) induces inflammatory cytokines and chemokines and triggers cell-mediated immune responses. The TLR-mediated signal pathway is important for mediating allograft rejection. We evaluated the effects of local knockdown of the TLR4 signaling pathway in a mouse segmental femoral graft model. Allografts were coated with freeze-dried lentiviral vectors that encoded TLR4 and myeloid differentiation primary response gene 88 (MyD88) short-hairpin RNA (shRNA), which were individually transplanted into the mice. They were assessed morphologically, radiographically, and histologically for tissue remodeling. Union occurred in autografted but not in allografted mice at the graft and host junctions after 4 weeks. TLR4 and MyD88 expression was up-regulated in allografted mice. TLR4 and MyD88 shRNAs inhibited TLR4 and MyD88 expression, which led to better union in the grafted sites. More regulatory T-cells in the draining lymph nodes suggested inflammation suppression. Local inhibition of TLR4 and MyD88 might reduce immune responses and ameliorate allograft rejection.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Knockdown of toll-like receptor 4 signaling pathways ameliorate bone graft rejection in a mouse model of allograft transplantation

Hsieh

Shen

et al. 2017

Sci Rep

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“…TLR signaling pathways trigger a series of interactions among specific intracellular mediators that ultimately result in the release of nuclear factor-κB (NF-κB) from its related endogenous inhibitors [11] . Earlier reports emphasized that markedly up-regulation of TLR2 and TLR4 responsible for early activation of alloimmune T-cells favoring to acute renal and also liver allograft rejection [28][29][30] . TLR2 was recently identified as a cell surface receptor activates secretion of inflammatory cytokine response to CMV infection [4,11] .…”

Section: Discussionmentioning

confidence: 99%

Role of cytomegalovirus on the maturation and function of monocyte derived dendritic cells of liver transplant patients

Karimi

Shariat

Yaghobi

et al. 2016

WJT

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AIM:To study the impact of association between cytomegalovirus (CMV) pathogenesis with dendritic cell (DC) maturation and function was evaluated in CMV reactivated liver transplanted patients in comparing with non-reactivated ones, and healthy controls. METHODS:Monocyte derived dendritic cells (MoDCs) was generated from collected ethylenediaminetetraacetic acid-treated blood samples from patient groups and controls. In these groups, expression rates and mean fluorescent intensity of DC markers were evaluated using flowcytometry technique. Secretion of cytokines including: interleukin (IL)-6, IL-12 and IL-23 were determined using enzyme-linked immunosorbent assay methods. The gene expression of toll-like receptor 2 (TLR2), TLR4 and IL-23 were analyzed using in-house real-time polymerase chain reaction protocols. RESULTS:Results have been shown significant decreases in: Expression rates of MoDC markers including CD83, CD1a and human leukocyte antigen DR (HLA-DR), the mean fluorescence intensitys for CD1a and HLA-DR, and secretion of IL-12 in CMV reactivated compared CONCLUSION: DC functional defects in CMV reactivated recipients, such as decrease in expression of DC maturation markers, increase in secretion of proinflammatory cytokines, and TLRs can emphasize on the importance of CMV infectivity in development of liver rejection in transplanted patients.

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“…2017; 17 (11):e12426. search, activation of innate immune system by the upregulation of IRF3 and TLR4 genes was detected in I/R injuries of hepatic acute rejection (47). In other words, IRF3 may amplify inflammatory response in liver transplant.…”

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confidence: 94%

Study the Cross-talk Between Hepatitis B Virus Infection and Interferon Regulatory Factors in Liver Transplant Patients

et al. 2017

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Background: Interferon regulatory factors (IRFs) as immunoregulatory molecules have a determinative antiviral role in liver transplantation outcomes and graft rejection. Hepatitis B virus (HBV) and its antigen derivatives also choose some strategies to escape from innate immune responses. Objectives: The current study aimed at evaluating inflammatory cross-talks between pattern recognition receptors (PRRs) signaling components such as IRF3 and IRF7 with HBV infection in mRNA levels in patients undergoing liver transplantation. Methods: The 46 HBV infected liver recipients were divided into rejection experienced (20) and not experienced (26) groups and a healthy control group was also considered. Peripheral mononuclear cells (PBMCs) were isolated form each studied patient on the days 1, 4, and 7 in post-transplant period. After RNA extraction and cDNA synthesis from each collected sample, the expression levels of IRF3 and IRF7 genes were evaluated using in-house SYBER Green based the real-time polymerase chain reaction (PCR) protocols. Results: The overexpression of mRNA levels of IRF3 (3.37 folds) and IRF7 (1.74 folds) on the day 1 were found in patients experiencing rejection, compared with non-rejected ones, based on initial ischemia/reperfusion (I/R) injuries. But, the mRNA levels of IRF3 (0.53 folds) and IRF7 (0.74 folds) on the day 4 were downregulated in patients with rejected transplantation, compared with non-rejected ones. Finally, reducing the expression of IRF3 (0.54 fold) on the day 7 and upregulation of IRF7 (2.38 fold) on the day 7 were found in rejected liver recipients, compared with non-rejected ones in post-transplant period. Conclusions: Downregulation of IRF3 expression in patients with HBV infection, who experienced rejection episodes in the first week post-liver transplantation indicated that they may be at higher risk for acute rejection; the hypothesis, which should be investigated in further studies.

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Acute allograft rejection in human liver transplant recipients is associated with signaling through toll‐like receptor 4

Cited by 42 publications

References 50 publications

Knockdown of toll-like receptor 4 signaling pathways ameliorate bone graft rejection in a mouse model of allograft transplantation

Knockdown of toll-like receptor 4 signaling pathways ameliorate bone graft rejection in a mouse model of allograft transplantation

Role of cytomegalovirus on the maturation and function of monocyte derived dendritic cells of liver transplant patients

Study the Cross-talk Between Hepatitis B Virus Infection and Interferon Regulatory Factors in Liver Transplant Patients

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