Curcumin Decreases Binding of Shiga-Like Toxin-1B on Human Intestinal Epithelial Cell Line HT29 Stimulated with TNF-α and IL-1β: Suppression of p38, JNK and NF-κB p65 as Potential Targets

Dong-Oh Moon; Cheng-Yun Jin; Jae-Dong Lee; Yung Hyun Choi; Soon-Cheol Ahn; Chang-Min Lee; Sang-Cheol Jeong; Yeong-Min Park; Gi-Young Kim

doi:10.1248/bpb.29.1470

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Curcumin Decreases Binding of Shiga-Like Toxin-1B on Human Intestinal Epithelial Cell Line HT29 Stimulated with TNF-α and IL-1β: Suppression of p38, JNK and NF-κB p65 as Potential Targets

Dong-Oh Moon, Cheng-Yun Jin, Jae-Dong Lee, Yung Hyun Choi, Soon-Cheol Ahn, Chang-Min Lee, Sang-Cheol Jeong, Yeong-Min Park, Gi-Young Kim

Author information

Dong-Oh Moon
Faculty of Applied Marine Science, Cheju National University
Cheng-Yun Jin
Department of Microbiology, College of Natural Sciences, Pusan National University
Jae-Dong Lee
Department of Microbiology, College of Natural Sciences, Pusan National University
Yung Hyun Choi
Department of Oriental Medicine, Dongeui University College of Oriental Medicine
Soon-Cheol Ahn
Department of Microbiology & Immunology, and National Research Laboratory of Dendritic Cell Differentiation & Regulation, Pusan National University College of Medicine
Chang-Min Lee
Department of Microbiology & Immunology, and National Research Laboratory of Dendritic Cell Differentiation & Regulation, Pusan National University College of Medicine
Sang-Cheol Jeong
Faculty of Applied Marine Science, Cheju National University
Yeong-Min Park
Department of Microbiology & Immunology, and National Research Laboratory of Dendritic Cell Differentiation & Regulation, Pusan National University College of Medicine
Gi-Young Kim
Faculty of Applied Marine Science, Cheju National University

Keywords: galactose-α1,4-galactose-β1,4-glucose ceramide, intestinal epithelial cell, Shiga-like toxin, curcumin

JOURNAL FREE ACCESS

2006 Volume 29 Issue 7 Pages 1470-1475

DOI https://doi.org/10.1248/bpb.29.1470

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Abstract

Intestinal epithelial cells (IECs) have been known to produce galactose-α1,4-galactose-β1,4-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-α and IL-1β. Additionally, curcumin was able to inhibit mitogen-activated protein kinases (MAPKs), such as p38 and JNK, but not ERK1/2, degradation of IκB or translocation of NF-κB 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-α and IL-1β and suggest that blocking of Stx-binding by curcumin may prevent the Stx-associated HUS.

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