Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway
<p>Resveratrol suppressed TNF-α-stimulated monocyte adhesion to EA.hy926 endothelial cells. The cells were pretreated with resveratrol (R, 1 µM, 5 µM, 20 µM) for 1 h prior to the addition of TNF-α (T, 10 ng/mL) for 24 h in the continued presence or absence of resveratrol. THP-1 cells were labeled with a fluorescence probe and the adhesion was determined using a microplate reader at excitation and emission wavelengths of 496 nm and 520 nm. T, TNF-α; R, Resveratrol. Values represent mean ± SEM, <span class="html-italic">n</span> = 3–5. *, <span class="html-italic">p</span> < 0.05 vs. control; #, <span class="html-italic">p</span> < 0.05 vs. TNF-α-alone-treated cells.</p> "> Figure 2
<p>Resveratrol reduced the expression of ICAM-1 (<b>A</b>) and CCL2 (<b>B</b>) in ECs. EA.hy926 cells were pretreated with various concentrations of resveratrol (R) for 1 h prior to the addition of TNF-α (T, 10 ng/mL) for 1 h in the continued presence or absence of resveratrol. The relative mRNA abundances of ICAM-1 and CCL2 were determined by real-time PCR and mean quantities were normalized based on the mean of housekeeping gene GAPDH. T, TNF-α; R, Resveratrol. Values represent mean ± SEM, <span class="html-italic">n</span> = 3. *, <span class="html-italic">p</span> < 0.05 vs. control; *, <span class="html-italic">p</span> < 0.05 vs. TNF-α-alone-treated cells. CCL2/MCP-1, monocyte chemoattractant protein-1; ICAM-1, soluble intercellular adhesion molecule-1.</p> "> Figure 3
<p>Resveratrol inhibited TNF-α-induced NF-κB signaling in HUVECs. (<b>A</b>) The cells were pretreated with 1 μm of resveratrol (R) for 1 h prior to the addition of TNF-α (T, 10 ng/mL) for 15 min in the continued presence or absence of resveratrol. Nuclear translocation of the NF-κB p65 subunit was visualized by immunofluorescence staining of ECs. Representative immunofluorescence fields show NF-κB p65 (green), nucleic acid with DAPI (blue), and overlay. (<b>B</b>) The nuclear and cytoplasmic fractions of p65 were quantified using a scoring system as described in Materials and Methods. *, <span class="html-italic">p</span> < 0.05 vs. control; #, <span class="html-italic">p</span> < 0.05 vs. TNF-α-alone-treated group.</p> "> Figure 4
<p>Dietary intake of resveratrol decreased monocyte binding to aortic endothelia (<b>A</b>), secretion of chemokines (<b>B</b>,<b>C</b>) and adhesion molecules (<b>D</b>,<b>E</b>) in the serum of TNF-α-treated mice. MCP-1/JE, CXCL1/KC, sICAM-1, and sVCAM-1 in serum were analyzed using ELISA. Values represent mean ± SEM. *, <span class="html-italic">p</span> < 0.05 vs. control; #, <span class="html-italic">p</span> < 0.05 vs. TNF-α-alone-treated mice. T, tumor necrosis factor-α; MCP-1/JE, mouse monocyte chemotactic protein 1/JE; CXCL1/KC, chemokine (C-X-C motif) ligand 1; sICAM-1, soluble intercellular adhesion molecule-1; sVCAM-1, soluble vascular adhesion molecule-1.</p> "> Figure 5
<p>Representative images showing the immunohistochemical staining for F4/80-positive monocyte-derived macrophages (<b>A</b>) and adhesion molecule VCAM-1 (<b>B</b>) in aortic cross-sections of C57BL/6 mice. C57BL/6 mice were fed AIN-93G rodent diets with and without 0.4% resveratrol for one week followed by 25 μg/kg/day of TNF-α injected intraperitoneally for 7 days. After the treatment periods, the animals’ aortas were harvested for sectioning. Quantitative analysis of F4/80- (<b>C</b>) and VCAM-1- (<b>D</b>) positive areas were performed. Arrows indicate typical positive-stained regions at a magnification of 40× (scale bar = 50 μm). T, TNF-α; R, resveratrol; T + R, TNF-α + resveratrol, * <span class="html-italic">p</span> < 0.05 vs. control; #, <span class="html-italic">p</span> < 0.05 vs. TNF-α-alone-treated mice.</p> "> Figure 6
<p>Representative aortic elastin fibers were visualized using Verhoeff–Van Gieson staining (magnification of 40×, scale bar = 50 μm). C57BL/6 mice were fed AIN-93G rodent diets with and without 0.4% resveratrol for one week followed by 25 μg/kg/day of TNF-α injected intraperitoneally for 7 days. After the treatment periods, the animals’ aortas were harvested for sectioning. T, TNF-α; R, resveratrol; T + R, TNF-α + resveratrol.</p> "> Figure 7
<p>Representative images showing the immunohistochemical staining for NF-κB p65 in aortic cross-sections (magnification of 40×, scale bar = 50 μm). C57BL/6 mice were fed AIN-93G rodent diets with and without 0.4% resveratrol for one week followed by 25 μg/kg/day of TNF-α injected intraperitoneally for 7 days. After treatment periods, the animals’ aortas were harvested for sectioning. Representative photomicrographs of immunohistochemical staining for NF-κB p65 (<b>A</b>). Quantitative analysis of NF-κB p65 (<b>B</b>). T, TNF-α; T+R, TNF-α + resveratrol. *, <span class="html-italic">p</span> < 0.05 vs. control; #, <span class="html-italic">p</span> < 0.05 vs. TNF-α-alone-treated mice.</p> ">
Abstract
:1. Introduction
2. Results
2.1. Resveratrol Reduced TNF-α-Induced Monocyte Adhesion to ECs
2.2. Resveratrol Suppressed Gene Expression of TNF-α-Induced Chemokine and Adhesion Molecules in ECs
2.3. Resveratrol Inhibits TNF-α-Induced NF-κB Activation in HUVECs
2.4. Dietary Ingestion of Resveratrol Suppresses TNF-α-Induced Vascular Inflammation In Vivo
2.5. Resveratrol Prevents TNF-α-Induced Disruption of Aortic Elastin Fiber in Mouse Aortic Cross-Sections
2.6. Resveratrol Diminishes TNF-α-Induced NF-κB Activation in Aortic Cross-Sections
3. Discussion
4. Materials and Methods
4.1. Chemicals and Materials
4.2. Cell Culture
4.3. Monocyte Adhesion Assay
4.4. Reverse Transcription and RT-PCR
4.5. Confocal Immunofluorescence Study of NF-κB p65 Nuclear Translocation
4.6. Animal and Experimental Design
4.7. Ex Vivo Monocyte Adhesion Assay
4.8. Measurements of Chemokines and Adhesion Molecules
4.9. Histology
4.10. Analysis pf VCAM-1, F4/80, and NF-κB p65 in Mice Aortas
4.11. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Nallasamy, P.; Kang, Z.Y.; Sun, X.; Anandh Babu, P.V.; Liu, D.; Jia, Z. Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway. Int. J. Mol. Sci. 2021, 22, 12486. https://doi.org/10.3390/ijms222212486
Nallasamy P, Kang ZY, Sun X, Anandh Babu PV, Liu D, Jia Z. Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway. International Journal of Molecular Sciences. 2021; 22(22):12486. https://doi.org/10.3390/ijms222212486
Chicago/Turabian StyleNallasamy, Palanisamy, Zi Yae Kang, Xiaolun Sun, Pon Velayutham Anandh Babu, Dongmin Liu, and Zhenquan Jia. 2021. "Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway" International Journal of Molecular Sciences 22, no. 22: 12486. https://doi.org/10.3390/ijms222212486