title: Curcumin decreases binding of Shiga-like toxin-1B on human intestinal epithelial cell line HT29 stimulated with TNF-alpha and IL-1beta: suppression of p38, JNK and NF-kappaB p65 as potential targets.
abstract: Intestinal epithelial cells (IECs) have been known to produce galactose-alpha1,4-galactose-beta1,4-glucose ceramide (Gb3) which plays a pivotal role in the mucosal immune response. In particular, Shiga-like toxins (Stx) can induce apoptosis of IECs in the development of hemolytic uremic syndrome (HUS) through binding on Gb3. Therefore, it has been hypothesized that down-regulation of Gb3 (or binding of Stx) prevents Stx from damaging in IECs. This study investigated whether curcumin, having various biological properties such as being anti-bacterial, anti-viral and anti-cancer, could decrease binding of Stx and the related signal pathway. Curcumin significantly inhibited the binding of Stx and the production of Gb3 synthase (GalT6) mRNA in HT29 IECs stimulated with TNF-alpha and IL-1beta. Additionally, curcumin was able to inhibit mitogen-activated protein kinases (MAPKs), such as p38 and JNK, but not ERK1/2, degradation of IkappaB or translocation of NF-kappaB p65. Furthermore, curcumin significantly attenuated Stx-1 induced cell death and IL-8 expression. In summary, these data link Gb3 expression in HT29 cells stimulated with TNF-alpha and IL-1beta and suggest that blocking of Stx-binding by curcumin may prevent the Stx-associated HUS.
authors.affiliation: Faculty of Applied Marine Science, Cheju National University, South Korea.
authors.forename: Dong-Oh
authors.initials: DO
authors.lastname: Moon
authors.forename: Cheng-Yun
authors.initials: CY
authors.lastname: Jin
authors.forename: Jae-Dong
authors.initials: JD
authors.lastname: Lee
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Soon-Cheol
authors.initials: SC
authors.lastname: Ahn
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Jeong
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022603:Shiga Toxins / Q000493:pharmacokinetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D022603:Shiga Toxins; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D003474:Curcumin