Hydroxytyrosol regulates the autophagy of vascular adventitial fibroblasts through the SIRT1-mediated signaling pathway

2018 ◽  
Vol 96 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Weirong Wang ◽  
Ting Jing ◽  
Xiaofeng Yang ◽  
Yanhao He ◽  
Bo Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Docking Studies ◽  
Sirtuin 1 ◽  
Autophagic Flux ◽  
Tnf Α ◽  
Adventitial Fibroblasts ◽  
Factor Α ◽  
Necrosis Factor ◽  
Inflammatory Effect

Hydroxytyrosol (HT), a phenolic compound in olive oil, exerts an anti-inflammatory effect in cardiovascular diseases. Recent studies found that autophagy was a therapeutic target of diseases. However, the effect of HT on autophagy in vascular adventitial fibroblasts (VAFs) remains unknown. Thus, in this study, we aimed to determine the effect of HT on cell autophagy and related signaling pathway and whether HT regulates the inflammatory response through autophagy in VAFs. Our results showed that HT promoted cell autophagy by increasing the conversion of LC3 and Beclin1 expression and the autophagic flux in VAFs stimulated with tumor necrosis factor-α (TNF-α). HT also upregulated the expression of the deacetylase sirtuin 1 (SIRT1) protein and mRNA compared with the TNF-α group. The molecular docking studies showed the good compatibility between HT and SIRT1, indicating that HT might act through SIRT1. Further study found that HT regulated autophagy through SIRT1-mediated Akt/mTOR suppression in VAFs. In addition, HT inhibited TNF-α-induced inflammatory response in VAFs through SIRT1. Furthermore, the study showed that HT inhibited the inflammatory response of VAFs through autophagy. These findings indicate that HT regulates the autophagy of VAFs through SIRT1-mediated Akt/mTOR suppression and then inhibits the inflammatory response of VAFs.

scholarly journals SIRT1 Regulates the Inflammatory Response of Vascular Adventitial Fibroblasts through Autophagy and Related Signaling Pathway

2017 ◽  
Vol 41 (2) ◽  
pp. 569-582 ◽  
Author(s):  
Wei-Rong Wang ◽  
Ting-Ting Li ◽  
Ting Jing ◽  
Yan-Xiang Li ◽  
Xiao-Feng Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Degradation Pathway ◽  
Sirtuin 1 ◽  
Akt Inhibitor ◽  
Cellular Survival ◽  
Akt Phosphorylation ◽  
Transmission Electron ◽  
Tnf Α ◽  
Adventitial Fibroblasts

Background/Aims: Autophagy is a lysosomal degradation pathway that is essential for cellular survival, differentiation, and homeostasis. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, plays a pivotal role in modulation of autophagy. Recent studies found that autophagy was involved in the regulation of inflammatory response. In this study, we aimed to determine the effect of SIRT1 on autophagy and inflammation, and whether autophagy can regulate the inflammatory response in vascular adventitial fibroblasts (VAFs). Methods: Cell autophagy was evaluated by fluorescence microscope and transmission electron microscopy. The expression of protein and mRNA were determined by Western blot analysis and real time-PCR. The production of cytokine was detected by ELISA. Results: TNF-α induced autophagy and increased SIRT1 expression in VAFs. SIRT1 activator resveratrol enhanced TNF-α-induced VAF autophagy. In contrast, SIRT1 knockdown attenuated VAF autophagy. Both the Akt inhibitor MK2206 and mTOR inhibitor rapamycin further increased TNF-α-induced VAF autophagy. Furthermore, SIRT1 knockdown increased Akt phosphorylation and inhibited the autophagy in VAFs. However, MK2206 attenuated the effect of SIRT1 knockdown on VAF autophagy. In addition, ingenuity pathway analysis showed that there is a relationship between cell autophagy and inflammation. We found that SIRT1 knockdown increased the expression of NLRP3 and interleukin (IL)-6 and promoted the production of IL-1β in VAFs. Further study showed that autophagy activation decreased the expression of NLRP3 and IL-6 and inhibited the production of IL-1β, whereas autophagy inhibition increased the inflammatory response of VAFs. More importantly, our study showed that autophagy was involved in the degradation of NLRP3 through the autophagy-lysosome pathway. Conclusion: SIRT1 not only regulates VAF autophagy through the Akt/mTOR signaling pathway but also suppresses the inflammatory response of VAFs through autophagy.

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

scholarly journals Propofol attenuated the effect of TNF-α on occludin expression by inhibiting HIF-1α/VEGF/VEGFR-2/ERK signaling pathway in hCMEC/D3 cells

2019 ◽  
Author(s):  
Yue Zhang ◽  
Xiaowei Ding ◽  
Changhong Miao ◽  
Jiawei Chen
Keyword(s):  
Signaling Pathway ◽  
Cell Counting ◽  
Erk Signaling ◽  
Microvascular Endothelial Cell ◽  
Tight Junction Proteins ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor ◽  
Junction Proteins

Abstract Purpose: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α(TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms. Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8. Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGF, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression. Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, which was attenuated by propofol.

scholarly journals Berry Phenolic and Volatile Extracts Inhibit Pro-Inflammatory Cytokine Secretion in LPS-Stimulated RAW264.7 Cells through Suppression of NF-κB Signaling Pathway

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 871
Author(s):  
Inah Gu ◽  
Cindi Brownmiller ◽  
Nathan B. Stebbins ◽  
Andy Mauromoustakos ◽  
Luke Howard ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Complex Mixture ◽  
Limited Information ◽  
Potential Health ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Raw264.7 Macrophage ◽  
Necrosis Factor

Berries are a rich source of phytochemicals, especially phenolics well known for protective activity against many chronic diseases. Berries also contain a complex mixture of volatile compounds that are responsible for the unique aromas of berries. However, there is very limited information on the composition and potential health benefits of berry volatiles. In this study, we isolated phenolic and volatile fractions from six common berries and characterized them by HPLC/HPLC-MS and GC/GC-MS, respectively. Berry phenolic and volatile fractions were evaluated for an anti-inflammatory effect using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells by measuring levels of pro-inflammatory cytokines and the nuclear factor-kappa B (NF-κB) signaling pathway. Results showed that LPS-induced excessive production of nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which were inhibited by berry phenolic and volatile extracts. Moreover, berry phenolic and volatile extracts reduced the nuclear translocation of NF-κB by blocking the phosphorylation of p65 and degradation of IκBα. These findings showed that berry volatiles from six berries had comparable anti-inflammatory effects to berry phenolics through the suppression of pro-inflammatory mediators and cytokines expression via NF-κB down-regulation, despite being present in the fruit at a lower concentration.

scholarly journals Propofol attenuated the effect of TNF-α on occludin expression by inhibiting HIF-1α/VEGF/VEGFR-2/ERK signaling pathway in hCMEC/D3 cells

2019 ◽  
Author(s):  
Yue Zhang ◽  
Xiaowei Ding ◽  
Changhong Miao ◽  
Jiawei Chen
Keyword(s):  
Signaling Pathway ◽  
Cell Counting ◽  
Erk Signaling ◽  
Microvascular Endothelial Cell ◽  
Tight Junction Proteins ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor ◽  
Junction Proteins

Abstract Background: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α(TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms. Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8. Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression. Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, which was attenuated by propofol.

scholarly journals Propofol attenuated the effect of TNF-α on occludin expression by inhibiting HIF-1α/VEGF/VEGFR-2/ERK signaling pathway in hCMEC/D3 cells

2019 ◽  
Author(s):  
Yue Zhang ◽  
Xiaowei Ding ◽  
Changhong Miao ◽  
Jiawei Chen
Keyword(s):  
Signaling Pathway ◽  
Cell Counting ◽  
Erk Signaling ◽  
Microvascular Endothelial Cell ◽  
Tight Junction Proteins ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor ◽  
Junction Proteins

Abstract Purpose: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α(TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms. Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8. Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGF, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression. Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, which was attenuated by propofol.

scholarly journals Tumour necrosis factor-α and adenosine in endotoxin shockleading related cardiovascular symptoms

1995 ◽  
Vol 4 (6) ◽  
pp. 454-455 ◽  
Author(s):  
S. Sipka ◽  
T. Seres ◽  
Z. Dinya ◽  
Z. Szekanecz ◽  
J. Szentmiklósi ◽  
...  
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Cardiogenic Shock ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Elevated Plasma ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

We have observed uncontrollable cardiogenic shock as a cardiovascular manifestation of systemic inflammatory response syndrome (SIRS) leading to death in a 62-year-old woman. The diagnosis of SIRS was based on the demonstration of endotoxinaemia, and highly elevated plasma levels of tumour necrosis factor (TNF)-α, and interleukin (IL)-10. We suggest that these cytokines may contribute to the terminal SIRS-related arrythmias, impaired myocardial contractility, as well as increased vascular permeability. In addition, the increased production of adenosine, a counter-regulatory mediator of inflammation, may also play a role in cardiodepression. We suggest a relationship between the action of TNF-α , IL-10 and adenosine in the pathogenesis of circulatory symptoms described above.

scholarly journals Propofol attenuated the effect of TNF-α on occludin expression by inhibiting HIF-1α/VEGF/VEGFR-2/ERK signaling pathway in hCMEC/D3 cells

2019 ◽  
Author(s):  
Yue Zhang ◽  
Xiaowei Ding ◽  
Changhong Miao ◽  
Jiawei Chen
Keyword(s):  
Signaling Pathway ◽  
Cell Counting ◽  
Erk Signaling ◽  
Microvascular Endothelial Cell ◽  
Tight Junction Proteins ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor ◽  
Junction Proteins

Abstract Background: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α(TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms. Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8. Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression. Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, which was attenuated by propofol.

scholarly journals LncRNA-AK149641 regulates the secretion of tumor necrosis factor-α in P815 mast cells by targeting the nuclear factor-kappa B signaling pathway

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yao Zhou ◽  
Li-na Gu ◽  
Jie Zhang ◽  
Jing Pan ◽  
Jia-min Zhang ◽  
...  
Keyword(s):  
Mast Cells ◽  
Tumor Necrosis Factor ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Factor Α ◽  
Necrosis Factor

Abstract Long noncoding RNAs play important roles in various biological processes. However, not much is known about their roles in inflammatory response. Mast cells, involved in innate and adaptive immunity, are one of the major effector cells in allergic inflammatory reactions and contribute to the pathogenesis of disorders, including asthma. In the present study, we aimed to verify and elucidate the function and possible role of a novel lncRNA, called lncRNA-AK149641, in the mechanism of lipopolysaccharide (LPS)-induced inflammatory response in P815 mast cells. The results showed that downregulating lncRNA-AK149641 decreased secretion of tumor necrosis factor-α into the supernatants of LPS-stimulated mast cells. Mechanistically, the activity of nuclear factor-kappa B (NF-κB) decreased after downregulating lncRNA-AK149641, as shown by western blot and electrophoretic mobility shift assays. Moreover, RNA binding protein immunoprecipitation (RIP) verified that lncRNA-AK149641 was able to bind to NF-κB in the nucleus. In conclusion, we demonstrated that lncRNA-AK149641 regulated LPS-induced inflammatory response in mast cells through the NF-κB signaling pathway.

scholarly journals Propofol attenuated the effect of TNF-α on occludin expression by inhibiting HIF-1α/VEGF/VEGFR-2/ERK signaling pathway in hCMEC/D3 cells

2019 ◽  
Author(s):  
Yue Zhang ◽  
Xiaowei Ding ◽  
Changhong Miao ◽  
Jiawei Chen
Keyword(s):  
Signaling Pathway ◽  
Cell Counting ◽  
Erk Signaling ◽  
Microvascular Endothelial Cell ◽  
Tight Junction Proteins ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Necrosis Factor ◽  
Junction Proteins

Abstract Purpose: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α(TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms. Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8. Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGF, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression. Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, which was attenuated by propofol.

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