The Experts below are selected from a list of 40416 Experts worldwide ranked by ideXlab platform
Reinhard Gruber - One of the best experts on this subject based on the ideXlab platform.
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Inhibitory effect of saliva on osteoclastogenesis in vitro requires Toll-Like Receptor 4 signaling
Clinical Oral Investigations, 2017Co-Authors: Heinz-dieter Müller, Jordi Caballé-serrano, Adrian Lussi, Reinhard GruberAbstract:Objectives Saliva can suppress osteoclastogenesis, but the underlying mechanism has not been discovered yet. Considering that endotoxins suppress osteoclastogenesis in bone marrow cultures and that saliva contains endotoxins, it was reasonable to hypothesize that the impact of saliva on osteoclastogenesis requires Toll-Like Receptor 4 signaling. Material and methods To test this hypothesis, we blocked Toll-Like Receptor 4 signaling with TAK-242 in the presence of saliva in murine bone marrow cultures. Osteoclastogenesis was evaluated based on gene expression analysis and histochemical staining for tartrate-resistant acid phosphatase. Resorption was performed on dentine. Results We report that TAK-242 reversed the inhibitory effect of fresh sterile saliva on the formation of multinucleated cells that stained positive for tartrate-resistant acid phosphatase. In line with this finding, TAK-242 increased the expression of the osteoclast functional genes cathepsin K, calcitonin Receptor, and tartrate-resistant acid phosphatase in the presence of saliva. TAK-242 also supported the expression of NFATc1, the master regulator of osteoclastogenesis, as well as DC-STAMP and Atp6v0d2, both being cell fusion genes. In support of the hypothesis, depletion of saliva from endotoxin partially reversed the inhibitory effect on osteoclastogenesis. Moreover, salivary pellicle on plastic and titanium did not affect osteoclastogenesis. Conclusion Inhibition of Toll-Like Receptor 4 signaling revealed that saliva can contribute to innate immunity by preventing hematopoietic progenitors to become osteoclasts. Clinical relevance Saliva can activate pattern recognition Receptor signaling through endotoxins and other stress factors, indicating the demand for macrophages rather than for osteoclasts.
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Inhibitory effect of saliva on osteoclastogenesis in vitro requires Toll-Like Receptor 4 signaling
Clinical oral investigations, 2017Co-Authors: Heinz-dieter Müller, Jordi Caballé-serrano, Adrian Lussi, Reinhard GruberAbstract:Saliva can suppress osteoclastogenesis, but the underlying mechanism has not been discovered yet. Considering that endotoxins suppress osteoclastogenesis in bone marrow cultures and that saliva contains endotoxins, it was reasonable to hypothesize that the impact of saliva on osteoclastogenesis requires Toll-Like Receptor 4 signaling. To test this hypothesis, we blocked Toll-Like Receptor 4 signaling with TAK-242 in the presence of saliva in murine bone marrow cultures. Osteoclastogenesis was evaluated based on gene expression analysis and histochemical staining for tartrate-resistant acid phosphatase. Resorption was performed on dentine. We report that TAK-242 reversed the inhibitory effect of fresh sterile saliva on the formation of multinucleated cells that stained positive for tartrate-resistant acid phosphatase. In line with this finding, TAK-242 increased the expression of the osteoclast functional genes cathepsin K, calcitonin Receptor, and tartrate-resistant acid phosphatase in the presence of saliva. TAK-242 also supported the expression of NFATc1, the master regulator of osteoclastogenesis, as well as DC-STAMP and Atp6v0d2, both being cell fusion genes. In support of the hypothesis, depletion of saliva from endotoxin partially reversed the inhibitory effect on osteoclastogenesis. Moreover, salivary pellicle on plastic and titanium did not affect osteoclastogenesis. Inhibition of Toll-Like Receptor 4 signaling revealed that saliva can contribute to innate immunity by preventing hematopoietic progenitors to become osteoclasts. Saliva can activate pattern recognition Receptor signaling through endotoxins and other stress factors, indicating the demand for macrophages rather than for osteoclasts.
Heinz-dieter Müller - One of the best experts on this subject based on the ideXlab platform.
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Inhibitory effect of saliva on osteoclastogenesis in vitro requires Toll-Like Receptor 4 signaling
Clinical Oral Investigations, 2017Co-Authors: Heinz-dieter Müller, Jordi Caballé-serrano, Adrian Lussi, Reinhard GruberAbstract:Objectives Saliva can suppress osteoclastogenesis, but the underlying mechanism has not been discovered yet. Considering that endotoxins suppress osteoclastogenesis in bone marrow cultures and that saliva contains endotoxins, it was reasonable to hypothesize that the impact of saliva on osteoclastogenesis requires Toll-Like Receptor 4 signaling. Material and methods To test this hypothesis, we blocked Toll-Like Receptor 4 signaling with TAK-242 in the presence of saliva in murine bone marrow cultures. Osteoclastogenesis was evaluated based on gene expression analysis and histochemical staining for tartrate-resistant acid phosphatase. Resorption was performed on dentine. Results We report that TAK-242 reversed the inhibitory effect of fresh sterile saliva on the formation of multinucleated cells that stained positive for tartrate-resistant acid phosphatase. In line with this finding, TAK-242 increased the expression of the osteoclast functional genes cathepsin K, calcitonin Receptor, and tartrate-resistant acid phosphatase in the presence of saliva. TAK-242 also supported the expression of NFATc1, the master regulator of osteoclastogenesis, as well as DC-STAMP and Atp6v0d2, both being cell fusion genes. In support of the hypothesis, depletion of saliva from endotoxin partially reversed the inhibitory effect on osteoclastogenesis. Moreover, salivary pellicle on plastic and titanium did not affect osteoclastogenesis. Conclusion Inhibition of Toll-Like Receptor 4 signaling revealed that saliva can contribute to innate immunity by preventing hematopoietic progenitors to become osteoclasts. Clinical relevance Saliva can activate pattern recognition Receptor signaling through endotoxins and other stress factors, indicating the demand for macrophages rather than for osteoclasts.
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Inhibitory effect of saliva on osteoclastogenesis in vitro requires Toll-Like Receptor 4 signaling
Clinical oral investigations, 2017Co-Authors: Heinz-dieter Müller, Jordi Caballé-serrano, Adrian Lussi, Reinhard GruberAbstract:Saliva can suppress osteoclastogenesis, but the underlying mechanism has not been discovered yet. Considering that endotoxins suppress osteoclastogenesis in bone marrow cultures and that saliva contains endotoxins, it was reasonable to hypothesize that the impact of saliva on osteoclastogenesis requires Toll-Like Receptor 4 signaling. To test this hypothesis, we blocked Toll-Like Receptor 4 signaling with TAK-242 in the presence of saliva in murine bone marrow cultures. Osteoclastogenesis was evaluated based on gene expression analysis and histochemical staining for tartrate-resistant acid phosphatase. Resorption was performed on dentine. We report that TAK-242 reversed the inhibitory effect of fresh sterile saliva on the formation of multinucleated cells that stained positive for tartrate-resistant acid phosphatase. In line with this finding, TAK-242 increased the expression of the osteoclast functional genes cathepsin K, calcitonin Receptor, and tartrate-resistant acid phosphatase in the presence of saliva. TAK-242 also supported the expression of NFATc1, the master regulator of osteoclastogenesis, as well as DC-STAMP and Atp6v0d2, both being cell fusion genes. In support of the hypothesis, depletion of saliva from endotoxin partially reversed the inhibitory effect on osteoclastogenesis. Moreover, salivary pellicle on plastic and titanium did not affect osteoclastogenesis. Inhibition of Toll-Like Receptor 4 signaling revealed that saliva can contribute to innate immunity by preventing hematopoietic progenitors to become osteoclasts. Saliva can activate pattern recognition Receptor signaling through endotoxins and other stress factors, indicating the demand for macrophages rather than for osteoclasts.
Paul Kubes - One of the best experts on this subject based on the ideXlab platform.
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platelets express functional toll like Receptor 4
Blood, 2005Co-Authors: Graciela Andonegui, Steven M Kerfoot, Kelly M Mcnagny, Kirsten V J Ebbert, Kamala D Patel, Paul KubesAbstract:Profound thrombocytopenia occurs in humans with sepsis and in mice administered lipopolysaccharide (LPS). Growing evidence indicates that platelets may contribute to these abnormalities, but whether that is a direct result of LPS activation of platelets or an indirect result of other inflammatory mechanisms remains unclear. Here we demonstrate that although platelets do not increase P-selectin expression in response to LPS, platelets bind more avidly to fibrinogen under flow conditions in a Toll-Like Receptor-4 (TLR4)-dependent manner. In addition, we find that CD41+ megakaryocytes grown from fetal livers and adult circulating platelets express significant amounts of TLR4. LPS induced thrombocytopenia in wild-type mice but not in TLR4-deficient (TLR4 def ) mice. Wild-type platelets accumulated in the lungs of wild-type mice in response to LPS; TLR4 def platelets did not. However, wild-type platelets did not accumulate in the lungs of LPS-treated TLR4 def mice. Neutrophils also accumulated in the lungs, and this preceded platelet accumulation. Neutrophil depletion completely abolished LPS-induced platelet sequestration into the lungs, but platelet depletion did not affect neutrophil accumulation. Thus, our data show for the first time that platelets do express functional levels of TLR4, which contribute to thrombocytopenia through neutrophil-dependent pulmonary sequestration in response to LPS. (Blood. 2005;106:2417-2423)
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Is there a role for cardiomyocyte Toll-Like Receptor 4 in endotoxemia?
Trends in cardiovascular medicine, 2005Co-Authors: Samantha A. Tavener, Paul KubesAbstract:Lipopolysaccharide (LPS) is thought to be an important molecule in myocardial depression in sepsis. Toll-Like Receptor 4 (TLR4), the lipopolysaccharide Receptor, is known to underlie these responses. Because TLR4 is expressed on both cardiac myocytes and immune cells, it is unclear as to which cell type is responsible for myocyte depression. In this article, we present evidence that the early response is likely related to TLR4 on immune cells and most likely macrophages, whereas the more delayed response may involve various immune cells as well as myocytes.
Steven P. Larosa - One of the best experts on this subject based on the ideXlab platform.
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Toll-Like Receptor-4 antagonist eritoran tetrasodium for severe sepsis.
Expert review of anti-infective therapy, 2011Co-Authors: Mark Tidswell, Steven P. LarosaAbstract:The human innate immune system initiates inflammation in response to bacterial molecules, particularly Gram-negative bacterial endotoxin. The steps by which endotoxin exposure leads to systemic inflammation include binding to Toll-Like Receptor-4 that specifically recognizes endotoxin and subsequently triggers cellular and molecular inflammatory responses. Severe sepsis is a systemic inflammatory response to infection that induces organ dysfunction and threatens a person's survival. Severe sepsis is frequently associated with increased blood levels of endotoxin. It is a significant medical problem that effects approximately 700,000 patients every year in the USA, resulting in 250,000 deaths. Eritoran tetrasodium is a nonpathogenic analog of bacterial endotoxin that antagonizes inflammatory signaling by the immune Receptor Toll-Like Receptor-4. Eritoran is being evaluated for the treatment of patients with severe sepsis.
Pierre-françois Laterre - One of the best experts on this subject based on the ideXlab platform.
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Toll-Like Receptor 4 Modulation as a Strategy to Treat Sepsis
Mediators of inflammation, 2010Co-Authors: Xavier Wittebole, Diego Castanares-zapatero, Pierre-françois LaterreAbstract:Despite a decrease in mortality over the last decade, sepsis remains the tenth leading causes of death in western countries and one of the most common cause of death in intensive care units. The recent discovery of Toll-Like Receptors and their downstream signalling pathways allowed us to better understand the pathophysiology of sepsis-related disorders. Particular attention has been paid to Toll-Like Receptor 4, the Receptor for Gram-negative bacteria outer membrane lipopolysaccharide or endotoxin. Since most of the clinical trial targeting single inflammatory cytokine in the treatment of sepsis failed, therapeutic targeting of Toll-Like Receptor 4, because of its central role, looks promising. The purpose of this paper is to focus on the recent data of various drugs targeting TLR4 expression and pathway and their potential role as adjunctive therapy in severe sepsis and septic shock.
