Inhibitory effects of epicatechin on interleukin-1β-induced inducible nitric oxide synthase expression in RINm5F cells and rat pancreatic islets by down-regulation of NF-κB activation

Myung Jun Kim, Gyeong Ryul Ryu, Jung Hoon Kang, Sang Soo Sim, Do Sik Min, Duck Joo Rhie, Shin Hee Yoon, Sang June Hahn, In Kyung Jeong, Kyong Ja Hong, Myung Suk Kim, Yang Hyeok Jo

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Cytokines that are released by infiltrating inflammatory cells around the pancreatic islets are involved in the pathogenesis of type 1 diabetes mellitus. Specifically, interleukin-1β (IL-1β) stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction, leading to the β-cell damage. In activating this pathway, nuclear factor-κB (NF-κB) plays a crucial role, and many of the IL-1β-sensitive genes contain NF-κB binding sites in their promoter regions. We have recently shown that epicatechin, which is a flavonoid, had a protective effect on pancreatic β-cells in both streptozotocin-treated rats and islets. In the present study, the effects of epicatechin on IL-1β-induced β-cell damage were examined. RINm5F cells and islets were pretreated with epicatechin and next incubated with IL-1β. The released nitrite, iNOS protein and mRNA expression levels were then measured. IκBα protein, nuclear translocation of NF-κB, and NF-κB 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-1β-induced nitrite production, iNOS protein and mRNA expressions, and it also inhibited IL-1β-induced IκBα protein degradation, NF-κB activation, and iNOS promoter activity. Epicatechin partly restored the IL-1β-induced inhibition of insulin release. These results suggest that epicatechin inhibits the IL-1β-induced iNOS expression by down-regulating NF-κB activation, and protecting β-cells from IL-1β.

Original languageEnglish
Pages (from-to)1775-1785
Number of pages11
JournalBiochemical Pharmacology
Issue number9
Publication statusPublished - 2004 Nov 1


All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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