Renal expression of Toll-like receptor 2 and 4: Dynamics in human allograft injury and comparison to rodents

Stribos, Elisabeth G. D.; Werkhoven, Maaike B. van; Poppelaars, Felix; Goor, Harry van; Olinga, Peter; Son, Willem J. van; Damman, Jeffrey; Seelen, Marc A.

doi:10.1016/j.molimm.2014.11.003

Cited by 10 publications

(14 citation statements)

References 37 publications

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“…The family of Toll-like receptors (TLRs)is pattern recognition receptors that recognize specific pathogen associated molecular patterns (PAMPs), which are found in pathogens but not in mammalian cells[ 40 ].TLRs are known to be highly expressed in innate immune cells in response to pathogens and environmental stressors[ 41 ]. Recently, TLRs have been found to express in renal tubular epithelial cells[ 17 ]. Emerging evidence suggests that endogenous ligands could activate TLRs, resulting in the antigen-independent inflammation that accompanies acute kidney injury (AKI), solid organ transplant rejection, and immune-mediated glomerulonephritis[ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…The Toll-like receptors (TLRs) are pattern recognition receptors and play a crucial role in regulating inflammatory response[ 15 , 16 ].Emerging studies described that innate immune activation through TLRs is an important driver in the pathogenesis of vascular remodelling and endothelial dysfunction, and renal injury [ 17 , 18 ]. Summers et al .…”

Section: Introductionmentioning

confidence: 99%

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TAK-242, a Toll-Like Receptor 4 Antagonist, Protects against Aldosterone-Induced Cardiac and Renal Injury

Zhang

Peng

et al. 2015

PLoS ONE

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Cardiovascular and renal inflammation induced by Aldosterone (Aldo) plays an important role in the pathogenesis of hypertension and renal fibrosis. Toll-like receptor 4 (TLR4) signaling contributes to inflammatory cardiovascular and renal diseases, but its role in Aldo-induced hypertension and renal damage is not clear. In the current study, rats were treated with Aldo-salt combined with TAK-242 (a TLR4 signaling antagonist) for 4 weeks. Hemodynamic, cardiac and renal parameters were assayed at the indicated time. We found that Aldo-salt–treated rats present cardiac and renal hypertrophy and dysfunction. Cardiac and renal expression levels of TLR4 as well as levels of molecular markers attesting inflammation and fibrosis are increased by Aldo infusion, whereas the treatment of TAK-242 reverses these alterations. TAK-242 suppresses cardiac and renal inflammatory cytokines levels (TNF-a, IL-1β and MCP-1). Furthermore, TAK-242 inhibits hypertension, cardiac and renal fibrosis, and also attenuates the Aldo-induced Epithelial-Mesenchymal Transition (EMT). In experimental hyperaldosteronism, upregulation of TLR4 is correlated with cardiac and renal fibrosis and dysfunction, and a TLR4 signaling antagonist, TAK-242, can reverse these alterations. TAK-242 may be a therapeutic option for salt-sensitive hypertension and renal fibrosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TAK-242, a Toll-Like Receptor 4 Antagonist, Protects against Aldosterone-Induced Cardiac and Renal Injury

Zhang

Peng

et al. 2015

PLoS ONE

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“…Expression of TLR-2 and TLR-4 increases due to ischemia-reperfusion injury in kidney transplants and the donor TLR-4 mediates ischemia-reperfusion injury [ 114 , 115 ]. TLR-2 and TLR-4 are constitutively expressed in the heart and drive ischemic injury to the heart in animal models of myocardial ischemia-reperfusion injury [ 69 , 113 ].…”

Section: The Innate Immune Response As a Potential Pharmacologicalmentioning

confidence: 99%

Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death

Toldo

Quader

Salloum

et al. 2016

IJMS

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Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response.

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“…Apoptosis and necrosis caused by IRI results in the release of damage associated molecular patterns (DAMPs) including self-nucleic acids, histones, and high mobility group protein B1. DAMPs can interact with pattern recognition receptors including Toll-like receptor (TLR) 2 and TLR4 expressed on myeloid cells 89, 90 , dendritic cells 89 , vascular endothelial cells 91, 92 , and tubular epithelial cells 93 . Ligation of TLRs results in the recruitment of MYD88 and the production of NF-κB.…”

Section: Introductionmentioning

confidence: 99%

The importance of non-HLA antibodies in transplantation

2016

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The development of post-transplant antibodies against non-HLA autoantigens is associated with rejection and decreased long-term graft survival. Although our knowledge of non-HLA antibodies is incomplete, recent studies provide compelling experimental and clinical findings demonstrating that antibodies directed against autoantigens contribute to the process of antibody-mediated acute and chronic rejection. Important areas for investigation remain understanding the mechanisms underlying the production of autoantibodies in the setting of organ transplantation. Ischaemia-reperfusion injury, surgical trauma and/or alloimmune responses can result in the release of organ-derived autoantigens in the form of soluble antigens, extracellular vesicles or apoptotic bodies that are presented in context of the transplant recipient’s antigen presenting cells to stimulate autoantibody production. Th17 cells are essential in the orchestrating autoantibody production by supporting the proliferation and maturation of autoreactive B cells within ectopic tertiary lymphoid tissue. Conversely, autoantibody-mediated graft damage can trigger alloimmunity and the development of donor-specific HLA antibodies that can act in synergy to promoteallograft rejection. Identification of the immunologic phenotypes of transplant recipients at risk of non-HLA antibody-mediated rejection and the development of targeted therapies to treat these rejections are sorely needed to improve both transplant and patient survival.

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Renal expression of Toll-like receptor 2 and 4: Dynamics in human allograft injury and comparison to rodents

Cited by 10 publications

References 37 publications

TAK-242, a Toll-Like Receptor 4 Antagonist, Protects against Aldosterone-Induced Cardiac and Renal Injury

TAK-242, a Toll-Like Receptor 4 Antagonist, Protects against Aldosterone-Induced Cardiac and Renal Injury

Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death

The importance of non-HLA antibodies in transplantation

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