Inhibitory effects of epicatechin on interleukin-1 beta-induced inducible nitric oxide synthase expression in RINm5F cells and rat pancreatic islets by down-regulation of NF-kappa B activation
- Authors
- Kim, MJ; Ryu, GR; Kang, JH; Sim, SS; Min, DS; Rhie, DJ; Yoon, SH; Hahn, SJ; Jeong, IK; Hong, KJ; Kim, MS; Jo, YH
- Issue Date
- Nov-2004
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- epicathechin; interleukin-1 beta; iNOS; NF-kappa B; RINm5F; islet
- Citation
- BIOCHEMICAL PHARMACOLOGY, v.68, no.9, pp 1775 - 1785
- Pages
- 11
- Journal Title
- BIOCHEMICAL PHARMACOLOGY
- Volume
- 68
- Number
- 9
- Start Page
- 1775
- End Page
- 1785
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/24741
- DOI
- 10.1016/j.bcp.2004.06.031
- ISSN
- 0006-2952
1873-2968
- Abstract
- Cytokines that are released by infiltrating inflammatory cells around the pancreatic islets are involved in the pathogenesis of type 1 diabetes mellitus. Specifically, interleukin-1beta (IL-1beta) stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction, leading to the beta-cell damage. In activating this pathway, nuclear factor-kappaB (NF-kappaB) plays a crucial role, and many of the IL-1beta-sensitive genes contain NF-kappaB binding sites in their promoter regions. We have recently shown that epicatechin, which is a flavonoid, had a protective effect on pancreatic beta-cells in both streptozotocin-treated rats and islets. In the present study, the effects of epicatechin on IL-1beta-induced beta-cell damage were examined. RINm5F cells and islets were pretreated with epicatechin and next incubated with IL-1beta. The released nitrite, iNOS protein and mRNA expression levels were then measured. IkappaBalpha protein, nuclear translocation of NF-kappaB, and NF-kappaB DNA binding activity were also determined. Following the transient transfection of an iNOS promoter into the cells, the iNOS promoter activity was measured. ATP- or D-glucose-induced insulin release was measured in RINm5F cells and islets, respectively. Epicatechin significantly reduced IL-1beta-induced nitrite production, iNOS protein and mRNA expressions, and it also inhibited IL-1beta-induced IkappaBalpha protein degradation, NF-kappaB activation, and iNOS promoter activity. Epicatechin partly restored the IL-1beta-induced inhibition of insulin release. These results suggest that epicatechin inhibits the IL-1beta-induced iNOS expression by down-regulating NF-kappaB activation, and protecting beta-cells from IL-1beta. (C) 2004 Elsevier Inc. All rights reserved.
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