title: Resveratrol induces nuclear factor-κB activity in human cardiac cells.
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.
  
  
  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-κB in AC16 cells, and exacerbated the increase caused by tumor necrosis factor-α (TNF-α). In accordance with this, resveratrol increased the expression of the pro-inflammatory genes ICAM-1 (intercellular adhesion molecule-1) and TNF-α. 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-κB p65 subunit levels were upregulated in an IκB-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-κB 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.
authors: Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona and IBUB, Institut de Biomedicina de la Universitat de Barcelona, 643 Diagonal, E-08028 Barcelona, Spain.
authors: Xavier
authors: X
authors: Palomer
authors: Eva
authors: E
authors: Capdevila-Busquets
authors: David
authors: D
authors: Alvarez-Guardia
authors: Emma
authors: E
authors: Barroso
authors: Mercè
authors: M
authors: Pallàs
authors: Antoni
authors: A
authors: Camins
authors: Mercy M
authors: MM
authors: Davidson
authors: Ana
authors: A
authors: Planavila
authors: Francesc
authors: F
authors: Villarroya
authors: Manuel
authors: M
authors: Vázquez-Carrera
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D013267:Stilbenes; D000077185:Resveratrol