Anthocyanins attenuate cytokine-induced responses during simultaneous exposure in immune and intestinal cells and reduce transglutaminase 2 expression

Celiac disease (CD) is a gluten-dependent chronic inflammatory disease. Anthocyanins (ACN) like cyanidin-3-glucoside (C3G) and delphinidin-3-glucoside (D3G) may possess anti-inflammatory properties. This study investigated their effects on cytokine-mediated inflammatory responses in Caco-2 intestinal epithelial and differentiated THP-1 cells. The cells were treated with C3G or D3G and stimulated with interferon-gamma (IFN-γ) or tumor necrosis factor-alpha (TNF-α). Inflammatory markers were analyzed at the gene expression and protein levels, and ACN stability was assessed by UHPLC-ESI-QqQ-MS/MS. D3G, but not C3G attenuated IFN-γ-induced monocyte chemoattractant protein-1 (MCP-1) and IFN-γ-induced protein 10 (IP-10) secretion in THP-1 cells as well as TNF-α-induced C-X-C motif chemokine ligand 1 (CXCL1), IP-10, and interleukin 8 (IL-8) secretion in Caco-2 cells. ACN pre-treatment also reduced transglutaminase 2 (TG2) mRNA expression in Caco-2 cells. Further analysis using a solid-phase IFNGR1-IFN-γ binding assay suggested interactions of C3G and D3G with the IFN-γ receptor. Overall, our results indicate that ACN, especially D3G, may modulate selected cytokine-induced inflammatory responses relevant to CD.