scholarly journals Angiopoietin-1 inhibits toll-like receptor 4 signalling in cultured endothelial cells: role of miR-146b-5p

2015 ◽  
Vol 106 (3) ◽  
pp. 465-477 ◽  
Author(s):  
Raquel Echavarria ◽  
Dominique Mayaki ◽  
Jean-Charles Neel ◽  
Sharon Harel ◽  
Veronica Sanchez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Cultured Endothelial Cells ◽  
Angiopoietin 1

Abstract 3932: Central Role Of Toll-like Receptor 4 In Oxidized Low Density Lipoprotein-and Lipopolysaccharide-Induced Bone Morphogenetic Protein-2 Expression In Human Coronary Artery Endothelial Cells

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Xin Su ◽  
Thomas R Johnson ◽  
Lihua Ao ◽  
Bruce L Paschall ◽  
Xiaoping Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Bone Morphogenetic Protein 2 ◽  
Toll Like Receptor ◽  
Oxidized Low Density Lipoprotein ◽  
Human Coronary Artery ◽  
Toll Like Receptor 4 ◽  
Morphogenetic Protein

Previous studies demonstrated that osteogenic mediators, in particular bone morphogenetic protein-2 (BMP-2), play an important role in the progression of atherosclerosis and vascular calcification. Although it is known that the atherogenic factor oxidized low density lipoprotein (oxLDL) up-regulates BMP-2 expression in endothelial cells, the signaling mechanisms involved are not well understood. In macrophages, oxLDL up-regulates Toll-like receptor 4 (TLR4) expression, and this innate immunoreceptor appears to be involved in oxLDL-induced macrophage actin polymerization. We earlier found that stimulation of TLR4 with lipopolysac-charide (LPS) increases cellular BMP-2 protein levels in human aortic valve interstitial cells. We hypothesized that the TLR4 pathway plays a central role in mediating BMP-2 expression in human coronary artery endothelial cells (CAECs). The purposes of this study were to examine whether TLR4 mediates oxLDL- and/or LPS-induced BMP-2 expression in human CAECs, and to determine whether the p38 and/or p44/42 MAPKs are involved. Methods and results : Stimulating human CAECs with LPS (E. coli 0111:B4, 200 ng/ml) for 24 h up-regulated BMP-2 protein expression. Similarly, stimulation with oxLDL (from human plasma, CuSO 4 -oxidized, LPS-free, 40–160 μg/ml) for 24 h induced BMP-2 expression in a dose-dependent manner. Pretreatment with either TLR4-neutralizing antibody or TLR4 siRNA significantly attenuated oxLDL-induced BMP-2 expression and abrogated the effect of LPS on BMP-2 expression. Over-expression of TLR4 enhanced the cellular BMP-2 response to oxLDL and LPS. Further, immunofluorescent staining co-localized oxLDL with TLR4. Although LPS induced ICAM-1 expression in human CAECs, oxLDL had no effect, indicating that oxLDL and LPS have different pro-inflammatory effects. BMP-2 expression was associated with activation of p38 and p44/42 MAPKs. Inhibiting p44/42, but not p38, reduced BMP-2 expression. Conclusions: In human CAECs, TLR4 plays a central role in regulating BMP-2 expression induced by either oxLDL or LPS, and the signaling mechanism involves the p44/42 MAPK pathway. These novel findings underscore an important role of TLR4 in atherosclerosis and vascular calcification.

scholarly journals Detrimental Role of Heat Shock Protein 60&70 and Toll-like Receptor 4 in Skeletal Muscle Ischaemia In Vitro

2013 ◽  
Vol 57 (5) ◽  
pp. 77S
Author(s):  
Ali Navi ◽  
Rebekah Yu ◽  
Xu Shi-Wen ◽  
Sidney Shaw ◽  
George Hamilton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 60 ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Muscle Ischaemia

Contrasting effects of the Toll-like receptor 4 in determining ovarian follicle endowment and fertility in female adult mice

Zygote ◽  
2021 ◽  
pp. 1-7
Author(s):  
Júlio Panzera Gonçalves ◽  
Breno Augusto Magalhães ◽  
Paulo Henrique Almeida Campos-Junior
Keyword(s):  
Ovarian Follicle ◽  
Cumulus Cells ◽  
Toll Like Receptor ◽  
Female Reproduction ◽  
Toll Like Receptor 4 ◽  
Genetic Ablation ◽  
Adult Mice ◽  
Cumulus Oocyte Complex ◽  
Estrous Cyclicity

Abstract Toll-like receptor 4 (TLR4) is best known for its role in bacteria-produced lipopolysaccharide recognition. Regarding female reproduction, TLR4 is expressed by murine cumulus cells and participates in ovulation and in cumulus–oocyte complex (COC) expansion, maternal–fetal interaction and preterm labour. Despite these facts, the role of TLR4 in ovarian physiology is not fully understood. Therefore, the aim of the present study was to investigate the effects of TLR4 genetic ablation on mice folliculogenesis and female fertility, through analysis of reproductive crosses, ovarian responsiveness and follicular quantification in TLR4−/− (n = 94) and C57BL/6 mice [wild type (WT), n = 102]. TLR4-deficient pairs showed a reduced number of pups per litter (P = 0.037) compared with WT. TLR4−/− mice presented more primordial, primary, secondary and antral follicles (P < 0.001), however there was no difference in estrous cyclicity (P > 0.05). A lower (P = 0.006) number of COC was recovered from TLR4−/− mice oviducts after superovulation, and in heterozygous pairs, TLR4−/− females also showed a reduction in the pregnancy rate and in the number of fetuses per uterus (P = 0.007) when compared with WT. Altogether, these data suggest that TLR4 plays a role in the regulation of murine folliculogenesis and in determining ovarian endowment. TLR4 deficiency may affect ovulation and pregnancy rates, potentially decreasing fertility, therefore the potential side effects of its blockade have to be carefully investigated.

Abstract 1766: Diet-Induced Obesity Causes Inflammation by Activating Toll-Like Receptor 4 Signaling and Downregulates AMPK in Heart

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hwi Jin Ko ◽  
Dae Young Jung ◽  
Zhexi Ma ◽  
Jason K Kim
Keyword(s):  
Glucose Metabolism ◽  
Whole Body ◽  
Chow Diet ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Myocardial Glucose Metabolism ◽  
Cardiac Inflammation ◽  
Protein Levels ◽  
Diet Induced Obesity

Increasing evidence implicates the role of inflammation in diabetes and complications. Macrophages are shown to infiltrate adipose tissue in obesity, and inflammatory cytokines alter glucose metabolism in peripheral organs. Male C57BL/6 mice were fed high-fat diet (HFD; 55% fat by calories) or chow diet for 6 weeks, and heart samples were taken for analysis (n = 5~7). Chronic HFD increased whole body fat mass, measured by 1 H-MRS, by 3-fold, and elevated plasma IL-6 and TNF-α levels by 40%. Diet-induced obesity caused inflammation in heart and increased macrophage-specific CD68 levels by 5-fold (Fig. 1) (* P < 0.05 vs Chow). Diet-induced cardiac inflammation was associated with significant increases in toll-like receptor 4 (TLR4) and MyD88 levels in heart (Fig. 2). HFD also increased cardiomyocyte SOCS3 levels by more than 3-fold (Fig. 3). Myocardial glucose metabolism was measured using intravenous injection of 2-[ 14 C]deoxyglucose in awake mice (n = 6). Chronic HFD reduced myocardial glucose uptake by 50%, and this was associated with significant reductions in total GLUT4 and GLUT1 protein levels. Further, Thr 172 phosphorylation of AMPK, a critical regulator of energy balance, was markedly reduced in heart following HFD (Fig. 4). These results demonstrate that diet-induced obesity causes macrophage infiltration and inflammation in heart by increasing TLR4 signaling in cardiomyocytes. Similar to the effects of inflammation on peripheral glucose metabolism, diet-induced cardiac inflammation reduced myocardial glucose metabolism by downregulating AMPK and GLUT protein levels. Thus, our findings underscore an important role of inflammation in diabetic heart.

Role of the toll-like receptor 4 polymorphism Asp299Gly in longevity and myocardial infarction in German men

2007 ◽  
Vol 128 (5-6) ◽  
pp. 409-411 ◽  
Author(s):  
Almut Nebel ◽  
Friederike Flachsbart ◽  
Arne Schäfer ◽  
Michael Nothnagel ◽  
Susanna Nikolaus ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4

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.

Sign in / Sign up

Export Citation Format

Share Document