Bilberry-derived anthocyanins prevent IFN-γ-induced pro-inflammatory signalling and cytokine secretion in human THP-1 monocytic cells.
OBJECTIVE
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.
Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
Sofia
S
Roth
Marianne R
MR
Spalinger
Isabelle
I
Müller
Silvia
S
Lang
Gerhard
G
Rogler
Michael
M
Scharl
D000818:Animals; D000872:Anthocyanins / Q000302:isolation & purification / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000737:chemistry; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000737:chemistry; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts; D011817:Rabbits; D050794:STAT1 Transcription Factor / Q000737:chemistry; D050796:STAT3 Transcription Factor / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D029800:Vaccinium myrtillus / Q000737:chemistry*
D000872:Anthocyanins; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D010936:Plant Extracts; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C073305:Vaccinium myrtillus extract; D020929:Mitogen-Activated Protein Kinase Kinases