Epigallocatechin-3-gallate suppresses galactose-α1,4-galactose-β1,4-glucose ceramide expression in TNFα stimulated human intestinal epithelial cells through inhibition of MAPKs and NF-κB

Intestinal epithelial cells (IECs) have been known to produce galactose-alpha 1,4-galactose-beta 1,4-glucose ceramide (Gb3) that play an important role in the mucosal immune response. The regulation of Gb3 is important to prevent tissue damage causing shiga like toxin. Epigallocatechin-3-gallate (EGCG) has been studied as anti-carcinogenic, anti-oxidant, anti-angiogenic, and anti-viral activities, and anti-diabetic. However, little is known between the expressions of Gb3 on IECs. The aim of this study was to examine the inhibitory effect of EGCG, a major ingredient of green tea, on Gb3 production via mitogen-activated protein kinases (MAPKs) and nuclear factor- kappa B (NF-kappa B) in the TNF-alpha stimulated human colon epithelial cells, HT29. To, investigate how Gb3 is regulated, ceramide glucosyltransferase (CGT), lactosylceramide synthase (GaIT2), and Gb3 synthase (GaIT6) were analyzed by RT-PCR in HT 29 cells exposed to TNF-alpha in the presence or absence of EGCG. EGGG dose-dependently manner, inhibits TNF-alpha induced Gb3 expression by blocking in both the MAPKs and NF-kappa B pathways in HT29 cells. TNF-alpha enhanced CGT, GaIT2 and GaIT6 mRNA levels and EGCG suppressed the level of these enzymes enhanced by TNF-alpha treatment.