Toc isomers modulation of inflammatory response in fhs 74 int fetal‐derived human intestinal cell line

The effect of α‐Tocopherol (Toc), γ‐Toc and δ‐Toc in modulating inflammatory response of fetal‐derived intestinal cell line (FHs 74 Int) were determined. Toc isomer‐dependently promoted interleukin (IL) 8 expression from FHs 74 Int cells, with δ‐Toc eliciting greatest pro‐inflammatory effect, followed by γ‐Toc and α‐Toc. The IL8 promoting activity was associated with non‐α‐Toc isomers ability to promote NfκB and Nrf‐2 activation as evidenced by the increased nuclear translocation of the transcription factors. Nevertheless, non‐α‐Toc isomers, particularly δ‐Toc, were found to down‐regulate the glutamate cysteine ligase (GCLC) gene expression, an Nrf‐2 target gene that is also the first and rate limiting enzyme involved in glutathione biosynthesis. The possibility that non‐α‐Toc isomers plays role in down‐regulating glutathione biosynthesis was evidenced by the finding that δ‐Toc and to a lesser extent γ‐Toc not only down‐regulated GCLC protein expression but also the total glutathione content of FHs 74 Int cells. Taken together, it is suggested that the down‐regulation of glutathione biosynthesis compromised the cellular defense system that leads to the pro‐inflammatory effect observed for the non‐α‐Toc isomers. Grant Funding Source : Food Nutrition and Health Vitamin Research Fund