scholarly journals Maslinic Acid Ameliorates Inflammation via the Downregulation of NF-κB and STAT-1

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 106 ◽  
Author(s):  
Wonhwa Lee ◽  
Jaehong Kim ◽  
Eui Kyun Park ◽  
Jong-Sup Bae
Keyword(s):  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Umbilical Vein ◽  
Lavage Fluid ◽  
Maslinic Acid ◽  
Tnf Α ◽  
Cox 2 ◽  
Umbilical Vein Endothelial Cells ◽  
Oxide Synthase ◽  
Necrosis Factor

Maslinic acid (MA), a natural compound of the triterpenoid group derived from olive, prevents the generation of pro-inflammatory cytokines and oxidative stress. In human umbilical vein endothelial cells (HUVECs) treated with lipopolysaccharide (LPS), we characterized the effects of MA on the regulation of heme oxygenase (HO)-1, cyclooxygenase (COX-)2, and inducible nitric oxide synthase (iNOS). MA was tested in the lung tissues of LPS-treated mice, to determine its effect on levels of iNOS expression and representative inflammatory mediators such as interleukin (IL)-1α and tumor necrosis factor (TNF)-α. We show that MA induced the expression of HO-1, reduced LPS-induced NF-κB-luciferase activity, and inhibited iNOS/NO and COX-2/PGE2, resulting in the downregulation of STAT-1 phosphorylation. Furthermore, our data show that MA induced the nuclear translocation of Nrf2, increased the binding of Nrf2 to ARE, and decreased IL-1α production in LPS-treated HUVECs. The MA-induced reduction in iNOS/NO expression was reversed by RNAi suppression of HO-1. In mice treated with LPS, MA significantly downregulated levels of iNOS in lung tissue and TNF-α in the bronchoalveolar lavage fluid. Taken together, our findings indicate that MA exerts a critical anti-inflammatory effect by modulating iNOS via the downregulation of NF-κB and p-STAT-1. Thus, we propose that MA may be an ideal substance to treat inflammatory diseases.

Tetrahydroxystilbene Glucoside Improves TNF-α-Induced Endothelial Dysfunction: Involvement of TGFβ/Smad Pathway and Inhibition of Vimentin Expression

2015 ◽  
Vol 43 (01) ◽  
pp. 183-198 ◽  
Author(s):  
Wenjuan Yao ◽  
Chengjing Gu ◽  
Haoran Shao ◽  
Guoliang Meng ◽  
Huiming Wang ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Nuclear Translocation ◽  
Cell Damage ◽  
Umbilical Vein ◽  
Polygonum Multiflorum ◽  
Vimentin Expression ◽  
Smad Signaling ◽  
Tnf Α ◽  
Umbilical Vein Endothelial Cells

Endothelial dysfunction plays an important role in the pathogenesis of atherogenesis. 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component of the rhizome extract from Polygonum multiflorum (PM), exhibits significant anti-atherosclerotic activity. Here, we used human umbilical vein endothelial cells (HUVECs) induced by tumor necrosis factor-α (TNF-α) in vitro to investigate the cytoprotective effects of TSG on TNF-α-induced endothelial injury and the related mechanisms. Pretreatment with 50 and 100 μM TSG markedly attenuated TNF-α-induced loss of cell viability and release of lactate dehydrogenase (LDH) and inhibited TNF-α-induced cell apoptosis. The inhibition of vimentin expression was involved in the cytoprotection afforded by TSG. Using inhibitors for PI3K and TGFβ or siRNA for Akt and Smad2, we found that vimentin production in HUVECs is regulated by TGFβ/Smad signaling, but not by PI3K–Akt–mTOR signaling. Meanwhile, TSG inhibited both the expression of TGFβ1 and the phosphorylation of Smad2 and Smad3, and TSG suppressed the nuclear translocation of Smad4 induced by TNF-α. These results suggest that TSG protects HUVECs against TNF-α-induced cell damage by inhibiting vimentin expression via the interruption of the TGFβ/Smad signaling pathway.

scholarly journals Baboon fetal arterial endothelial cells are more responsive to challenge by tumor necrosis factor α (TNF-α) than baboon fetal umbilical vein endothelial cells

2010 ◽  
Vol 212 (2) ◽  
pp. 701-703 ◽  
Author(s):  
A. Cerbulo-Vazquez ◽  
M. Zavala ◽  
G.A. Perez-Palacios ◽  
S.L. Jenkins ◽  
Luis D. Giavedoni ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Umbilical Vein ◽  
Tnf Α ◽  
Umbilical Vein Endothelial Cells ◽  
Factor Α ◽  
Arterial Endothelial Cells ◽  
Necrosis Factor

Anti-Inflammatory Activity ofSchizonepeta tenuifoliathrough the Inhibition of MAPK Phosphorylation in Mouse Peritoneal Macrophages

2008 ◽  
Vol 36 (06) ◽  
pp. 1145-1158 ◽  
Author(s):  
Su-Jin Kim ◽  
Jung-Sun Kim ◽  
In-Young Choi ◽  
Dong-Hyun Kim ◽  
Min-Cheol Kim ◽  
...  
Keyword(s):  
Peritoneal Macrophages ◽  
Mapk Phosphorylation ◽  
Inflammatory Reactions ◽  
Inflammatory Mechanism ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Mouse Peritoneal Macrophages ◽  
Necrosis Factor

Schizonepeta tenuifolia (ST) is a well-known herb to treat the cold and its associated headache. However, the anti-inflammatory mechanism of ST in mouse peritoneal macrophages is not clear. In this study, we demonstrated that ST inhibited lipopolysaccaride (LPS)-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. The maximal inhibition rate of TNF-α and IL-6 production by ST (2 mg/ml) was 48.01 ± 2.8% and 56.45 ± 2.8%, respectively. During the inflammatory process, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were increased in mouse peritoneal macrophages. However, treated with ST decreased the protein level of COX-2 and iNOS, as well as the production of PGE2and NO in LPS-stimulated mouse peritoneal macrophages. In addition, ST inhibited the phosphorylation of MAPK. Taken together, the results of this study suggest an important molecular mechanism by which ST reduces inflammation, which may explain its beneficial effect in the regulation of inflammatory reactions.

scholarly journals Protein Kinase Cϵ Is Required for Macrophage Activation and Defense Against Bacterial Infection

2001 ◽  
Vol 194 (9) ◽  
pp. 1231-1242 ◽  
Author(s):  
Antonio Castrillo ◽  
Daniel J. Pennington ◽  
Florian Otto ◽  
Peter J. Parker ◽  
Michael J. Owen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Bacterial Infection ◽  
Nuclear Translocation ◽  
Early Stage ◽  
Gram Positive Bacteria ◽  
Iκb Kinase ◽  
Tnf Α ◽  
Oxide Synthase ◽  
Necrosis Factor

To assess directly the role of protein kinase C (PKC)ϵ in the immune system, we generated mice that carried a homozygous disruption of the PKCϵ locus. PKCϵ−/− animals appeared normal and were generally healthy, although female mice frequently developed a bacterial infection of the uterus. Macrophages from PKCϵ−/− animals demonstrated a severely attenuated response to lipopolysaccharide (LPS) and interferon (IFN)γ, characterized by a dramatic reduction in the generation of NO, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. Further analysis revealed that LPS-stimulated macrophages from PKCϵ−/− mice were deficient in the induction of nitric oxide synthase (NOS)-2, demonstrating a decrease in the activation of IκB kinase, a reduction in IκB degradation, and a decrease in nuclear factor (NF)κB nuclear translocation. After intravenous administration of Gram-negative or Gram-positive bacteria, PKCϵ−/− mice demonstrated a significantly decreased period of survival. This study provides direct evidence that PKCϵ is critically involved at an early stage of LPS-mediated signaling in activated macrophages. Furthermore, we demonstrate that in the absence of PKCϵ, host defense against bacterial infection is severely compromised, resulting in an increased incidence of mortality.

Liver X receptor-α and miR-130a-3p regulate expression of sphingosine 1-phosphate receptor 2 in human umbilical vein endothelial cells

2016 ◽  
Vol 310 (3) ◽  
pp. C216-C226 ◽  
Author(s):  
Aihui Fan ◽  
Qian Wang ◽  
Yongjun Yuan ◽  
Jilun Cheng ◽  
Lixian Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Expression ◽  
Inflammatory Diseases ◽  
Umbilical Vein ◽  
Specific Inhibitor ◽  
Barrier Dysfunction ◽  
Human Umbilical Vein ◽  
Tnf Α ◽  
Sphingosine 1 Phosphate ◽  
Umbilical Vein Endothelial Cells

Recent studies have shown that activation of liver X receptors (LXRs) attenuates the development of atherosclerosis, not only by regulating lipid metabolism but also by suppressing inflammatory signaling. Sphingosine 1-phosphate receptor 2 (S1PR2), an important inflammatory gene product, plays a role in the development of various inflammatory diseases. It was proposed that S1PR2 might be regulated by LXR-α. In the present study, the effect of LXR-α on tumor necrosis factor-α (TNF-α)-induced S1PR2 expression in human umbilical vein endothelial cells (HUVECs) was investigated and the underlying mechanism was explored. The results demonstrated that TNF-α led to an increase in S1PR2 expression and triggered a downregulation of LXR-α expression in HUVECs as well. Downregulation of LXR-α with specific small interfering RNA (siRNA) remarkably enhanced the primary as well as TNF-α-induced expression of S1PR2 in HUVECs. Activation of LXR-α by agonist GW3965 inhibited both primary and TNF-α-induced S1PR2 expression. GW3965 also attenuated S1PR2-induced endothelial barrier dysfunction. The data further showed that TNF-α induced a significant decrease in miR-130a-3p expression. Overexpression of miR-130a-3p with mimic product reduced S1PR2 protein expression, and inhibition of miR-130a-3p by specific inhibitor resulted in an increase in S1PR2 protein expression. Furthermore, activation of LXRs with agonist enhanced the expression of miR-130a-3p, and knockdown of LXR-α by siRNA suppressed miR-130a-3p expression. These results suggest that LXR-α might downregulate S1PR2 expression via miR-130a-3p in quiescent HUVECs. Stimulation of TNF-α attenuates the activity of LXR-α and results in enhanced S1PR2 expression.

scholarly journals Lutonarin from Barley Seedlings Inhibits the Lipopolysacchride-Stimulated Inflammatory Response of RAW 264.7 Macrophages by Suppressing Nuclear Factor-κB Signaling

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1571
Author(s):  
Ji Yeong Yang ◽  
So-Yeun Woo ◽  
Mi Ja Lee ◽  
Hyun Young Kim ◽  
Jin Hwan Lee ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Nuclear Factor Κb ◽  
Ultra Performance Liquid Chromatography ◽  
Raw 264.7 ◽  
Nuclear Factor ◽  
Raw 264.7 Macrophages ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Necrosis Factor

Extracts from barley seedlings (BS) have known antioxidant and anti-inflammatory activities. The flavonoid lutonarin (LN) is a component of BS extract and has several known bioactivities. Here, we evaluated LN anti-inflammatory efficacy against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Lutonarin was isolated from BS by methanol extraction and characterized by ultra-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Lutonarin did not reduce the viability or enhance the apoptosis rate of RAW 264.7 macrophages at concentrations up to 150 µM. Concentrations within 20–60 µM dose-dependently suppressed the LPS-induced expression, phosphorylation, and nuclear translocation of the inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Furthermore, LN suppressed the LPS-induced upregulation of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α and of the inflammatory enzyme cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Lutonarin may be a safe and effective therapeutic agent for alleviation of pathological inflammation.

The Effect of Interleukin-4 on Tumour Necrosis Factor-Alpha Induced Expression of Tissue Factor and Plasminogen Activator Inhibitor-1 in Human Umbilical Vein Endothelial Cells

1993 ◽  
Vol 70 (06) ◽  
pp. 1037-1042 ◽  
Author(s):  
N B Martin ◽  
A Jamieson ◽  
D P Tuffin
Keyword(s):  
Tumour Necrosis ◽  
Umbilical Vein ◽  
Plasminogen Activator Inhibitor ◽  
Interleukin 4 ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tnf Α ◽  
Umbilical Vein Endothelial Cells ◽  
Activator Inhibitor ◽  
Necrosis Factor ◽  
Pai 1

SummaryThe pro-inflammatory cytokine tumour necrosis factor-a (TNF-α) is able to alter the haemostatic balance of human umbilical vein endothelial cells (HUVECs) towards that of a procoagulant and anti-fibrinolytic state. Treatment of HUVECs in culture with human recombinant TNF-α (0.5-50 U/ml; 6 h) significantly increased total cell expression of tissue factor (TF) 10-fold from 40 mU/well to 400-500 mU/well. Levels of plasminogen activator inhibitor-1 (PAI-1) antigen secreted from HUVECs also increased up to 2-fold in concentration-dependent fashion following addition of TNF-α (10-100 U/ml; 24 h). TNF-α induced total and cell surface expression of TF on HUVECs was significantly inhibited when the cells were pre-incubated with interleukin-4 (IL-4; p <0.001). This effect was time and concentration dependent. Pretreatment of HUVECs with IL-4 for 4 h had no significant effect, but increasing inhibition of total TF expression occurred after 8 and 16 h pre-incubations. Treatment with IL-4 at 20 and 200 U/ml significantly inhibited cell surface TF responses induced by TNF-α, whereas a low concentration (0.2 U/ml) was without effect. In contrast, the production of PAI-1 from HUVECs stimulated by TNF-α (50 U/ml) was unaffected by the presence and/or prior incubation with 200 U/ml IL-4. Thus, IL-4 may regulate the pro-coagulant but not the antifibrinolytic effects of TNF-α at sites of vascular inflammation.

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