Aspirin Action in Endothelial Cells: Different Patterns of Response Between Chemokine CX3CL1/CX3CR1 and TNF-α/TNFR1 Signaling Pathways

Szukiewicz, Dariusz; Wojciechowska, Małgorzata; Bilska, Anna; Stangret, Aleksandra; Szewczyk, Grzegorz; Mittal, Tarun; Wątroba, Mateusz; Kochanowski, Jan

doi:10.1007/s10557-015-6589-2

Cited by 11 publications

(6 citation statements)

References 45 publications

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“…As a proinflammatory, pleiotropic, and homotrimeric soluble cytokine, TNF-α is involved in various metabolic disorders, such as diabetes mellitus [38] and rheumatoid arthritis [39], and disorders with an inflammatory background, including, but not limited to, atherosclerosis [40]. TNF-α results in the initiation of transcriptional responses via the rapid activation of NF-κB [41]. Chronic inflammation is also a cardinal feature of atherosclerotic vascular disease, in which TNF-α causes endothelial dysfunction that leads to reduced vasodilatory responses [42].…”

Section: Discussionmentioning

confidence: 99%

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Zhang¹,

He²,

Shi³

2017

Cell Physiol Biochem

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Background/Aims: This study aimed to analyze the impact of microRNA-499 (miR-499) on the inflammatory damage of endothelial cells during coronary artery disease (CAD) via the targeting of PDCD4 through the NF-kB/ TNF-α signaling pathway. Methods: A total of 216 CAD patients (CAD group) and 90 healthy people (normal group) were enrolled in our study. Endothelial cells were collected and assigned into normal, OX-LDL, negative control (NC), miR-499 inhibitor, miR-499 mimic, PDCD4 siRNA, and miR-499 inhibitor + PDCD4 siRNA groups. The qRT-PCR and western blotting were performed to detect the mRNA and protein expression levels of PDCD4 and miR-499. The MTT assay was performed to determine cell viability, ELISA was performed to determine the expression levels of inflammatory factors, and flow cytometry assay to evaluate cell apoptosis. Results: Increased miR-499 expression and decreased PDCD4 expression in the plasma were observed in the CAD group compared with the normal group, demonstrating a negative correlation between miR-499 and PDCD4. Compared to the normal and miR-499 inhibitor groups, the survival rate of cells and PDCD4 expression were decreased; and the expressions of miR-499, IL-6, IL-8, IL-1β, TNF-α, NF-kB, VCAM-1, ICAM-1 and MCP-1 and the apoptosis rate were all elevated in the OX-LDL, NC, miR-499 mimic, PDCD4 siRNA and miR-499 inhibitor + PDCD4 siRNA groups. Compared to the OX-LDL, NC and miR-499 inhibitor + PDCD4 siRNA groups, PDCD4 expression and the survival rate of cells were increased; and the IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1 and MCP-1 expression levels and the apoptosis rate were all reduced in the miR-499 inhibitor group. In the PDCD4 siRNA group, PDCD4 expression and the survival rate of cells were lower, and the expression levels of IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1 and MCP-1 and the apoptosis rate were all higher compared with the miR-499 mimic group. In the miR-499 inhibitor + PDCD4 siRNA group, PDCD4 expression and the survival rate of cells were higher, and the expression levels of IL-6, IL-8, IL-1β, TNF-α, NF-κB, VCAM-1, ICAM-1, and MCP-1 and the apoptosis rate were all lower than those in the PDCD4 siRNA group. Conclusion: Down-regulated miR-499 expression increased PDCD4 expression and protected endothelial cells from inflammatory damage during CAD by inhibiting the NF-κB/TNF-α signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Zhang¹,

He²,

Shi³

2017

Cell Physiol Biochem

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“…The substance can also have anti-inflammatory effects by preventing the activation of NF-κB (31), associated with the inhibited activation of NF-κB kinase β by aspirin, decreasing the binding activity of NF-κB DNA (32). Studies have reported that aspirin exerts certain effects on NF-κB, IL-6, TNF-α, ICAM-1, CX3CL1 and CX3CR1, which is consistent with the findings of the present study (33,34). …”

Section: Discussionsupporting

confidence: 94%

Aspirin modulates the inflammatory response in a thrombus‑stimulated LMVEC model

Wang

Ying²,

Jiang

et al. 2018

Int J Mol Med

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The purpose of the present study was to examine whether aspirin interferes with the inflammatory response in a thrombus-stimulated lung microvascular endothelial cell (LMVEC) model. The LMVECs were randomly divided into eight groups: Normal group (group N), model group (group M), model + ASP group (group M+A), model+CX3CL1-short hairpin (sh)RNA group (group M+SH), model + CX3CL1-overexpression vector group (group M+CX3), model + ASP + shRNA group (group M+A+SH), model + ASP + CX3CL1-overexpression vector group (group M+A+CX3), and normal + virus control group (group N+V). The endothelial cells were cultured, and a thrombus was added to the cells. Briefly, 12 h following the precipitation of the thrombus, data from ELISA, reverse transcription-quantitative polymerase chain reaction analysis and confocal microscopy revealed that the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, CX3C chemokine ligand 1 (CX3CL1), CX3C chemokine receptor 1 (CX3CR1) and nuclear factor-κB (NF-κB) in group M were increased, compared with those in group N (P<0.01). These levels, with the exception of TNF-α, were significantly lower in group M+SH, compared with those in group M (P<0.01). Furthermore, the levels of IL-6 in groups M+A, M+CX3 and M+A+CX3 were decreased, compared with those in group M (P<0.01); the level of TNF-α in group M+A+SH was decreased, compared with that in group M (P<0.01); the level of CX3CR1 waslower in groups M+A and M+A+SH, compared with that in group M (P<0.01), and the level of NF-κB in group M+SH was decreased, compared with the level in group M and group M+A (P<0.05). In conclusion, the thrombus-stimulated LMVEC model exhibited induced production of TNF-α, IL-6, CX3CL, CX3CR1, NF-κB and intercellular adhesion molecule-1. Furthermore, it was confirmed that the signaling pathways involving CX3CL1-NF-κB, IL-6 and TNF-α were partly inhibited by aspirin.

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“…The activated NF-κB is transferred from the cytoplasm to the nucleus for transcription. It can transcribe a series of oncogenes related to cell growth and promote the production of tumors, so the activation condition of the NF-κB signaling pathway can be evaluated by NF-κB p65/50 (19,20). However, there are some shortcomings in this experiment.…”

Section: Discussionmentioning

confidence: 99%

Paeonol‑mediated apoptosis of hepatocellular carcinoma cells by NF‑κB pathway

Zhang

Sun

et al. 2018

Oncol Lett

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The aim of the study was to investigate the effect of paeonol on the apoptosis of hepatocellular carcinoma cells and to explore the possible mechanism of its effect. During the experiment, the human hepatoma (Huh7) cell line was cultured and treated with different concentrations of paeonol. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the effects of paeonol at different concentrations on the proliferation of Huh7 cells after 24 h, and the optimal concentration of paeonol was selected for follow-up experiments. Huh7 cells were divided into the blank control group (C group), parthenolide [(an inhibitor of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)] group (CE group), paeonol group (PO group), and paeonol + tumor necrosis factor-α (TNF-α) (an activator of NF-κB) group (PN group). The effect of paeonol on the apoptosis of Huh7 cells was detected via flow cytometry and Hoechst staining, respectively. The expression levels of NF-κB and protein apoptosis inhibitor-5 (p-API-5) were detected by semi-quantitative polymerase chain reaction (PCR) and western blot analysis, respectively, and the activity of NF-κB in cells was measured by NF-κB p65/50. After determination of the effects of paeonol at different concentrations on Huh7 cells by MTT assay, it was found that paeonol at the concentration of 200–800 µM could inhibit the proliferation of Huh7 cells (P<0.01), with 500 µM phenol being selected as the treatment concentration for follow-up experiments. Results of flow cytometry and Hoechst staining showed that the apoptotic levels of Huh7 cells in the PO and CE groups were significantly increased compared with that in the C group, and that in the PO group was higher than that in the PN group. The differences were statistically significant (P<0.01). Results of semi-quantitative PCR and western blot analysis revealed that the expression levels of NF-κB and p-API-5 in the PO and CE groups were significantly lower than those in the C group, and those in the PO group were lower than those in the PN group. The differences were statistically significant (P<0.01). The expression level of NF-κB p65/50 in the PO group was significantly lower than that in the C group (P<0.01). The results suggest that paeonol can significantly increase the apoptosis rate of Huh7 cells, and the possible mechanism of inducing apoptosis is related to the downregulation of NF-κB and p-API-5 and inhibition of the NF-κB signaling pathway.

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Aspirin Action in Endothelial Cells: Different Patterns of Response Between Chemokine CX3CL1/CX3CR1 and TNF-α/TNFR1 Signaling Pathways

Cited by 11 publications

References 45 publications

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Effects of MicroRNA-499 On the Inflammatory Damage of Endothelial Cells During Coronary Artery Disease Via the Targeting of PDCD4 Through the NF-Κβ/TNF-α Signaling Pathway

Aspirin modulates the inflammatory response in a thrombus‑stimulated LMVEC model

Paeonol‑mediated apoptosis of hepatocellular carcinoma cells by NF‑κB pathway

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