Anti-inflammatory mechanisms of resveratrol in activated HMC-1 cells: pivotal roles of NF-kappaB and MAPK

Pharmacol Res. 2009 May;59(5):330-7. doi: 10.1016/j.phrs.2009.01.009. Epub 2009 Jan 29.


Resveratrol is a phytoalexin polyphenolic compound found in various plants, including grapes, berries, and peanuts. Recently, studies have documented various health benefits of resveratrol including cardiovascular and cancer-chemopreventive properties. The aim of the present study was to demonstrate the effects of resveratrol on the expression of pro-inflammatory cytokines, as well as to elucidate its mechanism of action in the human mast cell line (HMC-1). Cells were stimulated with phorbol 12-myristate 13-acetate (PMA) plus A23187 in the presence or absence of resveratrol. To study the possible effects of resveratrol, ELISA, RT-PCR, real-time RT-PCR, Western blot analysis, fluorescence, and luciferase activity assays were used in this study. Resveratrol significantly inhibited the PMA plus A23187-induction of inflammatory cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. Moreover, resveratrol attenuated cyclooxygenase (COX)-2 expression and intracellular Ca2+ levels. In activated HMC-1 cells, phosphorylation of extra-signal response kinase (ERK) 1/2 decreased after treatment with resveratrol. Resveratrol inhibited PMA plus A23187-induced nuclear factor (NF)-kappaB activation, IkappaB degradation, and luciferase activity. Resveratrol suppressed the expression of TNF-alpha, IL-6, IL-8 and COX-2 through a decrease in the intracellular levels of Ca2+ and ERK 1/2, as well as activation of NF-kappaB. These results indicated that resveratrol exerted a regulatory effect on inflammatory reactions mediated by mast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Calcimycin / pharmacology
  • Calcium / metabolism
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Enzyme Activation
  • Humans
  • I-kappa B Kinase / antagonists & inhibitors
  • I-kappa B Kinase / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Mast Cells / drug effects*
  • Mast Cells / physiology
  • Mitogen-Activated Protein Kinases / physiology*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / physiology*
  • Phosphorylation
  • Resveratrol
  • Stilbenes / pharmacology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Stilbenes
  • Tumor Necrosis Factor-alpha
  • Calcimycin
  • Cyclooxygenase 2
  • I-kappa B Kinase
  • Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate
  • Resveratrol
  • Calcium