Food-derived bioactives as potential regulators of the IL-12/IL-23 pathway implicated in inflammatory bowel diseases.
Danesi F., Philpott M., Huebner C., Bordoni A., Ferguson LR.
The gene-specific modulation of inflammatory cytokines by food bioactives represents a possible approach to the nutritional or pharmaceutical prevention and treatment of inflammatory bowel disease (IBD). There is evidence for a key role of the interleukin-12beta1/23 receptor (IL-12 Rbeta1/23 R) pathway in IBD, and that reduction of the normal expression of the IL-23 R gene may provide a therapeutic target for this disease. The binding of interleukin-23 (IL-23) to its receptor IL-23 R regulates a newly defined effector T-cell subset, Th17 cells, characterised by the production of interleukin-17 (IL-17) and other cytokines, including tumour necrosis factor-alpha (TNF-alpha). In this study we developed an assay that measured IL-17 and TNF-alpha expression after incubation with specific dietary bioactives in the human T-cell Kit 225. It is anticipated that these changes will reflect differences in IL-23 R production, albeit indirectly. The cell line Kit 225 has similarities to Th17 cells, a subset of T cells producing IL-17 and TNF-alpha, and in initial experiments we demonstrated that the cells express both IL-23 receptor subunits, as well as IL-17 and TNF-alpha genes. Upon verification that stimulation of Kit 225 cells with 1ng/mL IL-23 significantly upregulated IL-17 and TNF-alpha gene expression, and IL-17 production, we supplemented cells with selected food bioactives, caffeic acid phenethyl ester (CAPE), epigallocatechin gallate (EGCG), docosahexaenoic acid (DHA), and linoleic acid (LA), and with phorbol myristate acetate (PMA) and sodium salicylate, used as pro-inflammatory and anti-inflammatory controls, respectively. In both unstimulated cells and after IL-23 stimulation, bioactives modulated the pro-inflammatory cytokines involved in IBD, underlining the possible role of foods in this disease. EGCG and DHA, which significantly inhibited both IL-17 and TNF-alpha expression, appeared particularly interesting.