Resveratrol attenuates ICAM-1 expression and monocyte adhesiveness to TNF-α-treated endothelial cells: evidence for an anti-inflammatory cascade mediated by the miR-221/222/AMPK/p38/NF-κB pathway

Abstract

Resveratrol, an edible polyphenolic phytoalexin, improves endothelial dysfunction and attenuates inflammation. However, the mechanisms have not been thoroughly elucidated. Therefore, we investigated the molecular basis of the effects of resveratrol on TNF-α-induced ICAM-1 expression in HUVECs. The resveratrol treatment significantly attenuated the TNF-α-induced ICAM-1 expression. The inhibition of p38 phosphorylation mediated the reduction in ICAM-1 expression caused by resveratrol. Resveratrol also decreased TNF-α-induced IκB phosphorylation and the phosphorylation, acetylation, and translocation of NF-κB p65. Moreover, resveratrol induced the AMPK phosphorylation and the SIRT1 expression in TNF-α-treated HUVECs. Furthermore, TNF-α significantly suppressed miR-221/-222 expression, which was reversed by resveratrol. miR-221/-222 overexpression decreased p38/NF-κB and ICAM-1 expression, which resulted in reduced monocyte adhesion to TNF-α-treated ECs. In a mouse model of acute TNF-α-induced inflammation, resveratrol effectively attenuated ICAM-1 expression in the aortic ECs of TNF-α-treated wild-type mice. These beneficial effects of resveratrol were lost in miR-221/222 knockout mice. Our data showed that resveratrol counteracted the TNF-α-mediated reduction in miR-221/222 expression and decreased the TNF-α-induced activation of p38 MAPK and NF-κB, thereby suppressing ICAM-1 expression and monocyte adhesion. Collectively, our results show that resveratrol attenuates endothelial inflammation by reducing ICAM-1 expression and that the protective effect was mediated partly through the miR-221/222/AMPK/p38/NF-κB pathway.

Minor compounds from virgin olive oil attenuate LPS‐induced inflammation via visfatin‐related gene modulation on primary human monocytes

“…In human monocytes, we found that all tested fractions or compounds of VOO reversed the reduction of SIRT1 gene expression caused by LPS. Our results match with those referred to the polyphenol resveratrol in TNF‐α treated human endothelial cells (Liu et al, ). Furthermore, we observed that the gene expression profile for PPAR γ was similar as to SIRT1 ; the UF, PF, and HTyr not only restoring but also potentiating PPAR γ gene expression in LPS‐treated human monocytes.…”

“…In human monocytes, we found that all tested fractions or compounds of VOO reversed the reduction of SIRT1 gene expression caused by LPS. Our results match with those referred to the polyphenol resveratrol in TNF-α treated human endothelial cells (Liu et al, 2017).…”

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

“…A recent clinical trial involving primary hypertensive patients evidenced that addition of a micronized formulation of RSV to standard antihypertensive therapy is sufficient to normalize the blood pressure, without additional antihypertensive drugs [127]. Other targets of RSV were identified by different other groups: TLR4 [128,129], miR-221/222 [130] and p38 MAPK [131,132].…”

Expression of silent information regulator 2 homolog 1 (SIRT1) in periapical granulomas

“…In addition, SIRT1 suppresses the NF-κB signaling pathway, thereby acting as an anti-inflammatory agent in persons with atherosclerosis, a chronic inflammatory disease (12). Interestingly, the SIRT1 activator resveratrol inhibits ICAM-1 expression in endothelial cells (13), Th2 cytokine expression in mast cells (14), and interleukin (IL)-1β-induced expression of matrix metalloproteinase-13 and IL-6 in articular chondrocytes (15). In addition, resveratrol decreases nitric oxide synthesis by hepatocytes (16), which suggests that SIRT1 activation by resveratrol ameliorates inflammation.…”