Resveratrol induces nuclear factor-kappaB activity in human cardiac cells.
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Palomer X, Capdevila-Busquets E, Alvarez-Guardia D, Barroso E, Pallas M, Camins A, Davidson MM, Planavila A, Villarroya F, Vazquez-Carrera M
Resveratrol induces nuclear factor-kappaB activity in human cardiac cells.
Int J Cardiol. 2013 Sep 10;167(6):2507-16. doi: 10.1016/j.ijcard.2012.06.006. Epub 2012 Jun 27.
- PubMed ID
- 22748497 [ View in PubMed]
- Abstract
BACKGROUND: Resveratrol is a grape polyphenol that prevents cardiac hypertrophy and protects the heart from ischemic injury, metabolic dysregulation, and inflammatory processes in several murine models. METHODS AND RESULTS: The aim of this study was to investigate the effects of resveratrol on the inflammatory processes in human cardiac AC16 cells in order to gain a better understanding of its cardioprotective mechanisms in the human heart. Resveratrol induced the DNA-binding activity of the pro-inflammatory transcription factor NF-kappaB in AC16 cells, and exacerbated the increase caused by tumor necrosis factor-alpha (TNF-alpha). In accordance with this, resveratrol increased the expression of the pro-inflammatory genes ICAM-1 (intercellular adhesion molecule-1) and TNF-alpha. In contrast, resveratrol decreased the expression of pro-inflammatory genes IL-6 (interleukin-6) and MCP-1 (monocyte chemoattractant protein-1). Likewise, resveratrol also induced inflammation in rat neonatal cardiomyocytes, and in the heart of mice fed a standard chow diet supplemented with resveratrol (1g/kg diet) for four months. Western-blot analyses revealed that NF-kappaB p65 subunit levels were upregulated in an IkappaB-dependent manner in the nuclei of resveratrol-treated human cardiac cells. Finally, resveratrol activated the signal transducer and activator of transcription 3 (STAT3) signaling and induced the expression of its anti-apoptotic downstream effector Bcl-xL, both involved in the cardioprotective survival activating factor enhancement (SAFE) pathway. CONCLUSIONS: Resveratrol enhanced NF-kappaB activity in human and murine cardiac cells, in a process that coincided with the activation of STAT3 and anti-apoptotic downstream effectors. Therefore, activation of the SAFE pathway by resveratrol might be involved in the cardioprotective effects of this compound.