Bilberry-derived anthocyanins prevent IFN-γ-induced pro-inflammatory signalling and cytokine secretion in human THP-1 monocytic cells

Digestion. 2014;90(3):179-89. doi: 10.1159/000366055. Epub 2014 Nov 12.

Abstract

Background/aims: Anthocyanins are plant-derived dietary components that are highly abundant, for example, in bilberries. We have previously demonstrated that anthocyanins exert anti-inflammatory properties in mouse colitis models and ameliorate disease activity in ulcerative colitis patients. Here, we studied the molecular mechanisms through which anthocyanin-containing bilberry extract (BE) exerts anti-inflammatory effects in human monocytic THP-1 cells.

Methods: THP-1 cells were pre-incubated with BE 20 min prior to TNF-α or IFN-γ (100 ng/ml each) stimulation. Signalling protein activation was studied by Western blotting, mRNA expression by quantitative PCR and cytokine secretion by ELISA.

Results: IFN-γ-induced phosphorylation of STAT1 and STAT3 was significantly reduced by BE co-treatment. Consequently, levels of mRNA expression and/or cytokine secretion of MCP-1, IL-6, TNF-α, ICAM-1, and T-bet were lower with BE co-treatment. In contrast, BE enhanced TNF-α-mediated p65-NF-κB phosphorylation but reduced ERK1/2 phosphorylation. BE co-treatment further increased TNF-α-induced mRNA expression and secretion of NF-κB target genes, such as IL-6, IL-8, and MCP-1, while mRNA levels of ICAM-1 were reduced.

Conclusions: BE co-treatment reduced IFN-γ-induced signal protein activation, pro-inflammatory gene expression, and cytokine secretion, whereas it enhanced TNF-α-induced responses. These findings suggest a distinct role for anthocyanins in modulating inflammatory responses that need to be further studied to fully understand anthocyanin-mediated effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthocyanins / isolation & purification
  • Anthocyanins / pharmacology*
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line
  • Cytokines / metabolism*
  • Drug Synergism
  • Gene Expression / drug effects
  • Humans
  • Interferon-gamma / antagonists & inhibitors*
  • Interferon-gamma / pharmacology
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / chemistry
  • Monocytes / drug effects*
  • Monocytes / immunology
  • NF-kappa B / chemistry
  • Phosphorylation / drug effects
  • Rabbits
  • STAT1 Transcription Factor / chemistry
  • STAT3 Transcription Factor / chemistry
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Vaccinium myrtillus / chemistry*

Substances

  • Anthocyanins
  • Anti-Inflammatory Agents
  • Cytokines
  • NF-kappa B
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Vaccinium myrtillus extract
  • Mitogen-Activated Protein Kinase Kinases