title: Epigallocatechin-3-gallate suppresses galactose-alpha1,4-galactose-1beta,4-glucose ceramide expression in TNF-alpha stimulated human intestinal epithelial cells through inhibition of MAPKs and NF-kappaB.
abstract: Intestinal epithelial cells (IECs) have been known to produce galactose-alpha1,4-galactose-beta1,4-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-kappaB (NF-kappaB) in the TNF-alpha stimulated human colon epithelial cells, HT29. To investigate how Gb3 is regulated, ceramide glucosyltransferase (CGT), lactosylceramide synthase (GalT2), and Gb3 synthase (GalT6) were analyzed by RT-PCR in HT 29 cells exposed to TNF-alpha in the presence or absence of EGCG. EGCG dose-dependently manner, inhibits TNF-alpha induced Gb3 expression by blocking in both the MAPKs and NF-kappaB pathways in HT29 cells. TNF-alpha enhanced CGT, GalT2 and GalT6 mRNA levels and EGCG suppressed the level of these enzymes enhanced by TNF-alpha treatment.
authors.affiliation: Department of Microbiology and Immunology, Pusan National University College of Medicine, Busan, Korea.
authors.forename: Dong-Oh
authors.initials: DO
authors.lastname: Moon
authors.forename: Se-Rim
authors.initials: SR
authors.lastname: Choi
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005700:Galactosyltransferases / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005964:Glucosyltransferases / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014281:Trihexosylceramides / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D014281:Trihexosylceramides; D014409:Tumor Necrosis Factor-alpha; C018549:globotriaosylceramide; D002392:Catechin; C045651:epigallocatechin gallate; D005700:Galactosyltransferases; D005964:Glucosyltransferases; C045097:UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase; C023235:glucosylceramide beta-1-4-galactosyltransferase; C023246:ceramide glucosyltransferase; D020928:Mitogen-Activated Protein Kinases