scholarly journals Activation of adult rat CNS endothelial cells by opioid-induced toll-like receptor 4 (TLR4) signaling induces proinflammatory, biochemical, morphological, and behavioral sequelae

Neuroscience ◽  
2014 ◽  
Vol 280 ◽  
pp. 299-317 ◽  
Author(s):  
P.M. Grace ◽  
K.M. Ramos ◽  
K.M. Rodgers ◽  
X. Wang ◽  
M.R. Hutchinson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
Adult Rat ◽  
Behavioral Sequelae ◽  
Rat Cns

scholarly journals Porphyromonasgingivalis Lipopolysaccharide Antagonizes Escherichiacoli Lipopolysaccharide at Toll-Like Receptor 4 in HumanEndothelialCells

2003 ◽  
Vol 71 (12) ◽  
pp. 6799-6807 ◽  
Author(s):  
Stephen R. Coats ◽  
Robert A. Reife ◽  
Brian W. Bainbridge ◽  
Thu-Thao T. Pham ◽  
Richard P. Darveau
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Adaptor Protein ◽  
Dominant Negative ◽  
Toll Like Receptor ◽  
Human Endothelial Cells ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
E Coli ◽  
Signaling Complex

ABSTRACT E. coli lipopolysaccharide (LPS) induces cytokine and adhesion molecule expression via the toll-like receptor 4 (TLR4) signaling complex in human endothelial cells. In the present study, we investigated the mechanism by which Porphyromonas gingivalis LPS antagonizes E. coli LPS-dependent activation of human endothelial cells. P. gingivalis LPS at 1 μg/ml inhibited both E. coli LPS (10 ng/ml) and Mycobacterium tuberculosis heat shock protein (HSP) 60.1 (10 μg/ml) stimulation of E-selectin mRNA expression in human umbilical vein endothelial cells (HUVEC) without inhibiting interleukin-1 beta (IL-1β) stimulation. P. gingivalis LPS (1μ g/ml) also blocked both E. coli LPS-dependent and M. tuberculosis HSP60.1-dependent but not IL-1β-dependent activation of NF-κB in human microvascular endothelial (HMEC-1) cells, consistent with antagonism occurring upstream from the TLR/IL-1 receptor adaptor protein, MyD88. Surprisingly, P. gingivalis LPS weakly but significantly activated NF-κB in HMEC-1 cells in the absence of E. coli LPS, and the P. gingivalis LPS-dependent agonism was blocked by transient expression of a dominant negative murine TLR4. Pretreatment of HUVECs with P. gingivalis LPS did not influence the ability of E. coli LPS to stimulate E-selectin mRNA expression. Taken together, these data provide the first evidence that P. gingivalis LPS-dependent antagonism of E. coli LPS in human endothelial cells likely involves the ability of P. gingivalis LPS to directly compete with E. coli LPS at the TLR4 signaling complex.

Toll-like receptor 4 in lymphatic endothelial cells contributes to LPS-induced lymphangiogenesis by chemotactic recruitment of macrophages

Blood ◽  
2009 ◽  
Vol 113 (11) ◽  
pp. 2605-2613 ◽  
Author(s):  
Shinae Kang ◽  
Seung-Pyo Lee ◽  
Kyung Eun Kim ◽  
Hak-Zoo Kim ◽  
Sylvie Mémet ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lymphatic Vessel ◽  
Immune Cell ◽  
Lymphatic Vessels ◽  
Nuclear Factor Κb ◽  
Cell Trafficking ◽  
Lymphatic Endothelial Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling

The lymphatic vessel is a major conduit for immune cell transport; however, little is known about how lymphatic vessels regulate immune cell trafficking and how lymphatic vessels themselves respond to inflammation. Toll-like receptor 4 (TLR4) plays a central role in lipopolysaccharide (LPS)–induced inflammation, but the role of TLR4 in lymphatic endothelial cells (LECs) is poorly understood. Here, we found that LECs express high amounts of TLR4 in the intracellular region, and that the TLR4 of LECs is the main mediator of nuclear factor–κB (NF-κB) activation by LPS. LPS-TLR4 signaling in LECs resulted in the production of various chemokines for chemotaxis of macrophage. In addition, TLR4 in LECs actively contributed to the recruitment of macrophages to the draining lymphatic vessel. Furthermore, the macrophages that infiltrated into the lymphatic vessel induced lymphangiogenesis by secreting lymphangiogenic growth factors. These phenomena were largely attenuated not only in the mice defective in TLR4 signaling but also in the chimeric mice defective in TLR4 signaling that were recipients for bone marrow transplantation from normal TLR4-signaling mice. In conclusion, TLR4 in LECs plays an essential role in LPS-induced inflammatory lymphangiogenesis by chemotactic recruitment of macrophages.

Absence of toll-like receptor 4 (TLR4) signaling in the donor organ reduces ischemia and reperfusion injury in a murine liver transplantation model

2007 ◽  
Vol 13 (10) ◽  
pp. 1435-1443 ◽  
Author(s):  
Xiu-Da Shen ◽  
Bibo Ke ◽  
Yuan Zhai ◽  
Feng Gao ◽  
Sei-Ichiro Tsuchihashi ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Ischemia And Reperfusion ◽  
Toll Like Receptor ◽  
Donor Organ ◽  
Ischemia And Reperfusion Injury ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
Murine Liver ◽  
Transplantation Model

scholarly journals TNF-α Activates High-Mobility Group Box 1 - Toll-Like Receptor 4 Signaling Pathway in Human Aortic Endothelial Cells

2016 ◽  
Vol 38 (6) ◽  
pp. 2139-2151 ◽  
Author(s):  
Won Seok Yang ◽  
Nam Jeong Han ◽  
Jin Ju Kim ◽  
Mee Jeong Lee ◽  
Su-Kil Park
Keyword(s):  
Signal Transduction ◽  
Endothelial Cells ◽  
High Mobility ◽  
Neutralizing Antibody ◽  
High Mobility Group ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Aortic Endothelial Cells ◽  
Tnf Α ◽  
Human Aortic Endothelial Cells

Background/Aims: Toll-like receptor 4 (TLR4) interacts with endogenous substances as well as lipopolysaccharide. We explored whether TLR4 is implicated in tumor necrosis factor-α (TNF-α) signal transduction in human aortic endothelial cells. Methods: The pathway was evaluated by transfection of siRNAs, immunoprecipitation and Western blot analysis. Results: TNF-α activated spleen tyrosine kinase (Syk) within 10 min, which led to endothelin-1 (ET-1) production. TLR4 was also rapidly activated by TNF-α stimulation, as shown by recruitment of interleukin-1 receptor-associated kinase 1 to TLR4 and its adaptor molecule, myeloid differentiation factor 88 (MyD88). siRNA depletion of TLR4 markedly attenuated TNF-α-induced Syk activation and ET-1 production. TLR4 inhibitor (CLI-095), TLR4-neutralizing antibody and siRNA depletion of MyD88 also attenuated TNF-α-induced Syk activation. Syk was co-immunoprecipitated with TLR4, and TNF-α activated Syk bound to TLR4. High-mobility group box 1 (HMGB1) was rapidly released and associated with TLR4 after TNF-α stimulation with a peak at 5 min, which was prevented by N-acetylcysteine, an antioxidant. Glycyrrhizin (HMGB1 inhibitor), HMGB1-neutralizing antibody and siRNA depletion of HMGB1 all suppressed TNF-α-induced Syk activation and ET-1 production. Conclusion: Upon TNF-α stimulation, TLR4 is activated by HMGB1 that is immediately released after the generation of reactive oxygen species, and plays a crucial role in the signal transduction.

scholarly journals ADAM17-Mediated Ectodomain Shedding of Toll-Like Receptor 4 as a Negative Feedback Regulation in Lipopolysaccharide-Activated Aortic Endothelial Cells

2018 ◽  
Vol 45 (5) ◽  
pp. 1851-1862 ◽  
Author(s):  
Won Seok Yang ◽  
Jin Ju Kim ◽  
Mee Jeong Lee ◽  
Eun Kyoung Lee ◽  
Su-Kil Park
Keyword(s):  
Endothelial Cells ◽  
P38 Mapk ◽  
Ectodomain Shedding ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Toll Like Receptor 4 ◽  
Negative Feedback Regulation ◽  
Mapk Activation ◽  
Aortic Endothelial Cells ◽  
Aortic Endothelial

Background/Aims: Lipopolysaccharide (LPS)-activated monocytes/macrophages develop endotoxin tolerance in part by reducing cell surface toll-like receptor 4 (TLR4) through cluster of differentiation 14 (CD14)-dependent endocytosis. In case of endothelial cells, CD14 is expressed in low copy numbers as compared with monocytes/macrophages. Thus, we explored how endothelial cells regulate TLR4 expression after LPS stimulation. Methods: Cultured human aortic endothelial cells (HAECs) were treated with LPS. TLR4 expression was analyzed by Western blot analysis and immunofluorescence staining. A disintegrin and metalloprotease 17 (ADAM17) activity was measured using a fluorescent substrate. Results: TLR4 in cell lysate began to decrease within 30 min of LPS treatment with a maximal reduction at 2 h, and it was accompanied by an increase of N-terminal fragment of TLR4 in culture supernatant, indicating ectodomain shedding of the receptor. LPS activated p38 mitogen-activated protein kinase (p38 MAPK) and ADAM17, while LPS-induced ADAM17 activation was inhibited by SB203580, a p38 MAPK inhibitor. LPS-induced ectodomain shedding of TLR4 was attenuated by siRNA depletion of ADAM17 as well as TAPI-2 (an inhibitor of ADAM family) and SB203580. LPS pretreatment resulted in a blunted response of p38 MAPK activation to further LPS stimulation. In the cells depleted of ADAM17, LPS-induced p38 MAPK activation was prolonged and LPS-induced intercellular adhesion molecule-1 expression was potentiated. Conclusion: HAECs respond to LPS by rapid shedding of the ectodomain of TLR4 and thereby reduce the responsiveness to subsequent LPS exposure. ADAM17, downstream of p38 MAPK, is implicated in the ectodomain cleavage of TLR4.

scholarly journals Toll-Like Receptor 4 Signaling and Drug Addiction

2020 ◽  
Vol 11 ◽  
Author(s):  
Ruyan Wu ◽  
Jun-Xu Li
Keyword(s):  
Drug Addiction ◽  
Multiple Drug ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
Drug Classes ◽  
Downstream Effectors ◽  
Potential Efficacy ◽  
Proinflammatory Responses

The emphasis of neuronal alterations and adaptations have long been the main focus of the studies of the mechanistic underpinnings of drug addiction. Recent studies have begun to appreciate the role of innate immune system, especially toll-like receptor 4 (TLR4) signaling in drug reward-associated behaviors and physiology. Drugs like opioids, alcohol and psychostimulants activate TLR4 signaling and subsequently induce proinflammatory responses, which in turn contributes to the development of drug addiction. Inhibition of TLR4 or its downstream effectors attenuated the reinforcing effects of opioids, alcohol and psychostimulants, and this effect is also involved in the withdrawal and relapse-like behaviors of different drug classes. However, conflicting results also argue that TLR4-related immune response may play a minimal part in drug addiction. This review discussed the preclinical evidence that whether TLR4 signaling is involved in multiple drug classes action and the possible mechanisms underlying this effect. Moreover, clinical studies which examined the potential efficacy of immune-base pharmacotherapies in treating drug addiction are also discussed.

scholarly journals Key Player in Cardiac Hypertrophy, Emphasizing the Role of Toll-Like Receptor 4

2020 ◽  
Vol 7 ◽  
Author(s):  
Zheng Xiao ◽  
Bin Kong ◽  
Hongjie Yang ◽  
Chang Dai ◽  
Jin Fang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cardiac Hypertrophy ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
New Technologies ◽  
Immune Cell ◽  
Current Knowledge ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling

Toll-like receptor 4 (TLR4), a key pattern recognition receptor, initiates the innate immune response and leads to chronic and acute inflammation. In the past decades, accumulating evidence has implicated TLR4-mediated inflammatory response in regulation of myocardium hypertrophic remodeling, indicating that regulation of the TLR4 signaling pathway may be an effective strategy for managing cardiac hypertrophy's pathophysiology. Given TLR4's significance, it is imperative to review the molecular mechanisms and roles underlying TLR4 signaling in cardiac hypertrophy. Here, we comprehensively review the current knowledge of TLR4-mediated inflammatory response and its interaction ligands and co-receptors, as well as activation of various intracellular signaling. We also describe the associated roles in promoting immune cell infiltration and inflammatory mediator secretion, that ultimately cause cardiac hypertrophy. Finally, we provide examples of some of the most promising drugs and new technologies that have the potential to attenuate TLR4-mediated inflammatory response and prevent or reverse the ominous cardiac hypertrophy outcomes.

scholarly journals Amphiphilic Guanidinocalixarenes Inhibit Lipopolysaccharide (LPS)- and Lectin-Stimulated Toll-like Receptor 4 (TLR4) Signaling

2017 ◽  
Vol 60 (12) ◽  
pp. 4882-4892 ◽  
Author(s):  
Stefania E. Sestito ◽  
Fabio A. Facchini ◽  
Ilaria Morbioli ◽  
Jean-Marc Billod ◽  
Sonsoles Martin-Santamaria ◽  
...  
Keyword(s):  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling

Atorvastatin suppresses LPS-induced rapid upregulation of Toll-like receptor 4 and its signaling pathway in endothelial cells

2011 ◽  
Vol 300 (5) ◽  
pp. H1743-H1752 ◽  
Author(s):  
Ying Wang ◽  
Ming Xiang Zhang ◽  
Xiao Meng ◽  
Fu Qiang Liu ◽  
Guang Sheng Yu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Umbilical Vein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Mapk Phosphorylation ◽  
Tlr4 Mrna

In the present study, we tested our hypothesis that atorvastatin exerts its anti-inflammation effect via suppressing LPS-induced rapid upregulation of Toll-like receptor 4 (TLR4) mRNA and its downstream p38, ERK, and NF-κB signaling pathways in human umbilical-vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs). TLR4 mRNA expression and its downstream kinase activities induced by LPS alone or atorvastatin + LPS in endothelial cells were quantified using quantitative real-time PCR and enzyme-linked immunosorbent assay. Preincubation of LPS-stimulated endothelial cells with TLR4 siRNA was conducted to identify the target of the anti-inflammatory effects of atorvastatin. Atorvastatin incubation resulted in the reduction of LPS-induced TLR4 mRNA expression, ERK1/2 and P38 MAPK phosphorylation, and NF-κB binding activity. Pretreatment with MEK/ERK1/2 inhibitor PD98059 attenuated atorvastatin + LPS-induced NF-κB activity but had no effect on P38 MAPK phosphorylation. In contrast, pretreatment with P38 MAPK inhibitor SB203580 resulted in upregulation of atorvastatin + LPS-induced ERK1/2 phosphorylation but had no significant effects on NF-κB activity. On the other hand, blocking NF-κB with SN50 produced no effects on atorvastatin + LPS-induced ERK1/2 and P38 MAPK phosphorylation. Moreover, TLR4 gene silencing produced the same effects as the atorvastatin treatment. In conclusion, atorvastatin downregulated TLR4 mRNA expression by two distinct signaling pathways. First, atorvastatin stabilized Iκ-Bα, which directly inhibited NF-κB activation. Second, atorvastatin inactivated ERK phosphorylation, which indirectly inhibited NF-κB activation. Suppression of p38 MAPK by atorvastatin upregulates ERK but exerts no effect on NF-κB.

399 INVOLVEMENT OF TOLL LIKE RECEPTOR-4 IN INFLAMMATORY RESPONSES OF ENDOTHELIAL CELLS

2011 ◽  
Vol 12 (1) ◽  
pp. 85
Author(s):  
R. Menghini ◽  
M. Tesauro ◽  
V. Rovella ◽  
A. Marino ◽  
R. Lauro ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4
Sign in / Sign up

Export Citation Format

Share Document