Bilberry-Derived Anthocyanins Prevent IFN-γ-Induced Pro-Inflammatory Signalling and Cytokine Secretion in Human THP-1 Monocytic Cells

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-a 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-a, ICAM-1, and T-bet were lower with BE co-treatment. In contrast, BE enhanced TNF-a-mediated p65-NF-γB phosphorylation but reduced ERK1/2 phosphorylation. BE co-treatment further increased TNF-a-induced mRNA expression and secretion of NF-γB 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-a-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.

Anthocyanins Prevent Colorectal Cancer Development in a Mouse Model

“…In human monocytic THP-1 cells, bilberry extract reduced interferon-γ (IFN-γ)-induced signal protein activation, pro-inflammatory gene expression and cytokine secretion, and enhanced tumor necrosis factor-α (TNF-α)-induced responses [28] . Even a recent study on biopsy samples of patients with ulcerative colitis treated with an oral anthocyanin-rich bilberry preparation during an open label clinical trial revealed reduced amounts of the proinflammatory cytokines IFN-γ and TNF-α [29] .…”

Docosahexaenoic acid inhibits 12-O-tetradecanoylphorbol-13- acetate-induced fascin-1-dependent breast cancer cell migration by suppressing the PKCδ- and Wnt-1/β-catenin-mediated pathways

“…Furthermore, EGCG induces apoptosis and suppresses pancreatic cancer cell growth, metastasis by suppressing STAT3 transcription and activation [ 66 ]. In human THP-1 monocytic cells, the inhibition by anthocyanins of IFNγ-activated STAT3 decreases IL-6, tumor necrosis factor α (TNFα), and intercellular adhesion molecule 1 (ICAM-1) secretion [ 67 ]. Targeting to β-catenin and STAT3α is thus an effective approach against metastasis in human colon, prostate, and breast cancer cells [ 68 , 69 ].…”

Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits

“…On the contrary, the control trial reveals no significant reduction in TNF-α level between the treatment and placebo at the end of the study (week-24). Another study also indicates that treatment of human monocytic THP-1 cells with 10 mg/ml anthocyanin-containing bilberry extract (25% anthocyanin content) significantly lowered IFN-γ-induced (100 ng/ml) expressions of MCP-1, IL-6, TNF-α, intercellular adhesion molecule 1 (ICAM-1), and T-cell-specific T-box transcription factor (T-bet) [159]. …”