Resveratrol protects late endothelial progenitor cells from TNF-α-induced inflammatory damage by upregulating Kr�ppel-like factor-2

Abstract

Cardiovascular risk factors can negatively influence late endothelial progenitor cell (EPCs) number and functions, thus EPCs biology is a clinical implications for cardiovascular diseases. The present study aimed to investigate the potential protective effects of resveratrol (RES) on tumor necrosis factor (TNF)-α-induced inflammatory damage in late endothelial progenitor cells (EPCs) and to elucidate the underlying mechanisms. Late EPCs at passages 3–5 were pretreated with RES at a concentration of 20 µmol/l for 12 h and subsequently incubated with TNF-α (10 ng/ml) for 24 h. The adhesion, migration, proliferation and vasculogenesis of EPCs were subsequently detected. Furthermore, the mRNA expression levels of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Nitric oxide (NO) levels in the supernatant were determined using a colorimetric assay kit. Additionally, the mRNA and protein expression of Krüppel-like factor-2 (KLF2) was determined by RT-qPCR and western blot analysis, respectively. The results indicated that TNF-α markedly inhibited the proliferation, adhesion, migration and vasculogenesis of late EPCs. However, RES ameliorated the effects induced by TNF-α. Furthermore, exposure of EPCs to TNF-α decreased the levels of NO secretion and KLF2 expression at the mRNA and protein levels, but upregulated the levels of inflammatory factors, including ICAM-1 and MCP-1, compared with the control group. RES significantly inhibited TNF-α-induced inflammatory damage through upregulation of KLF2 expression and downregulation of the expression of ICAM-1 and MCP-1. In conclusion, RES may exert protective effects on the cardiovascular system, as demonstrated by the amelioration of TNF-α-induced inflammation in EPCs following RES treatment, and may therefore be used in the future for the prevention of cardiovascular disease.

Total Polyphenol Intake Is Inversely Associated with a Pro/Anti-Inflammatory Biomarker Ratio in European Adolescents of the HELENA Study

“…The findings on IL-4 and IL-5 corroborate the Th1 to Th2 ratio findings as they are major effector cytokines secreted by Th2 (45). The anti-inflammatory activity of resveratrol [which was the most abundant stilbene in the HELENA study (12)] has previously been reflected by increased IL-4 in a retrospective study (46) and decreased TNF-α in an in vitro study (47), making the positive association with sVCAM-1 rather contradictory.…”

Direct and Indirect Inhibition Effects of Resveratrol against Toxoplasma gondii Tachyzoites In Vitro

“…However, neither resveratrol nor pyrimethamine was able to regulate the production of this cytokine significantly, despite the trend toward a slight decrease that we observed. Resveratrol has been considered a powerful anti-inflammatory compound that is expected to reduce the production of inflammatory cytokines, such as TNF-␣ and IL-1␤, in most of the cases examined by many researchers (44,45). However, it is noteworthy that a few studies reported that resveratrol could also regulate this cytokine in the opposite way.…”

Control of Inflammation by Calorie Restriction Mimetics: On the Crossroad of Autophagy and Mitochondria

“…Inflammaging dampening Aged humans [93] Autophagy-mitochondria AMPK and Sirt1 activation Worm, mouse [99,100] Pro-inflammatory cytokine levels decrease Mouse, humans [95,98] Anti-inflammatory T cell increase T cells [112] Adhesion molecule repression Endothelial cells [115][116][117][118] Resveratrol Inflammation NF-κB inhibition Macrophages, microglia [111,121] Autophagy-mitochondria AMPK and Sirt1 activation Worm, mouse [125] Mitochondria mtROS production decrease Mouse [127] Adhesion molecule repression Vascular endothelial cells [129] SASP blockade Senescent cells [131] NF-κB and JNK inhibition Mouse [132] Memory T cell differentiation Mouse [136] Pro-inflammatory cytokine expression and immune cell infiltration blockade Mouse brain [137,146,147] Microglia activation inhibition Mouse brain [139] Metformin…”

“…Thus, resveratrol attenuates inflammation in human umbilical vein endothelial cells (HUVEC) cells by a mechanism that depends on the Sirt1 mediated activation of autophagy [116]. Resveratrol also decreases the levels of important adhesion molecules, such as ICAM-1, in TNF-α stimulated endothelial progenitor cells [117] and HUVEC cells [118].…”