A Mechanism for the Action of the Compound DA-6034 on NF-kappa B Pathway Activation in Helicobacter pylori-Infected Gastric Epithelial Cells

Abstract

DA-6034 is a synthetic derivative of eupatilin, a flavonoid with anti-inflammatory effects. The aim of this study was to investigate the effects of DA-6034 on the interactions between I kappa B kinase (IKK) and heat shock protein 90 (Hsp90), and activation of the nuclear factor-kappaB (NF-kappa B) signalling pathway in human gastric epithelial cells infected with Helicobacter pylori. MKN-45 gastric epithelial cell line was treated with DA-6034 and H. pylori. DA-6034 significantly inhibited NF-kappa B activation and upregulated the expressions of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 in MKN-45 cells infected with H. pylori. However, DA-6034 did not influence activator protein-1 DNA binding activity in H. pylori-infected gastric epithelial cells. Pretreatment with DA-6034 attenuated the H. pylori-induced increase in IKK activity, and Hsp90 was associated with IKK-alpha and IKK-gamma in MKN-45 cells. Treatment with DA-6034 dissociated the Hsp90 and IKK-gamma complex in H. pylori-infected cells, leading to the inhibition of IL-8 expression. These results suggest that the eupatilin derivative 7-carboxymethyloxy-3',4',5-trimethoxy flavone has anti-inflammatory activity in gastric epithelial cells infected with H. pylori through the promotion of the dissociation of the IKK-gamma-Hsp90 complex and suppression of NF-kappa B signalling.