title: A mechanism for the action of the compound DA-6034 on NF-κB 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 IκB kinase (IKK) and heat shock protein 90 (Hsp90), and activation of the nuclear factor-kappaB (NF-κB) 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-κB 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-α and IKK-γ in MKN-45 cells. Treatment with DA-6034 dissociated the Hsp90 and IKK-γ 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-γ-Hsp90 complex and suppression of NF-κB signalling.
authors.affiliation: Department of Microbiology, Hanyang University College of Medicine, Seoul, KoreaDepartment of Biotechnology, Joongbu University, Choongnam, KoreaResearch Laboratory, Dong-A Pharmaceutical Company, Kyunggi-do, KoreaDepartment of Food and Nutrition, Yonsei University, Seoul, KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Ko
authors.affiliation: Department of Microbiology, Hanyang University College of Medicine, Seoul, KoreaDepartment of Biotechnology, Joongbu University, Choongnam, KoreaResearch Laboratory, Dong-A Pharmaceutical Company, Kyunggi-do, KoreaDepartment of Food and Nutrition, Yonsei University, Seoul, KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: D Y
authors.initials: DY
authors.lastname: Yoo
authors.affiliation: Department of Microbiology, Hanyang University College of Medicine, Seoul, KoreaDepartment of Biotechnology, Joongbu University, Choongnam, KoreaResearch Laboratory, Dong-A Pharmaceutical Company, Kyunggi-do, KoreaDepartment of Food and Nutrition, Yonsei University, Seoul, KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Hanyang University College of Medicine, Seoul, KoreaDepartment of Biotechnology, Joongbu University, Choongnam, KoreaResearch Laboratory, Dong-A Pharmaceutical Company, Kyunggi-do, KoreaDepartment of Food and Nutrition, Yonsei University, Seoul, KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: S M
authors.initials: SM
authors.lastname: Choi
authors.affiliation: Department of Microbiology, Hanyang University College of Medicine, Seoul, KoreaDepartment of Biotechnology, Joongbu University, Choongnam, KoreaResearch Laboratory, Dong-A Pharmaceutical Company, Kyunggi-do, KoreaDepartment of Food and Nutrition, Yonsei University, Seoul, KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: K K
authors.initials: KK
authors.lastname: Kang
authors.affiliation: Department of Microbiology, Hanyang University College of Medicine, Seoul, KoreaDepartment of Biotechnology, Joongbu University, Choongnam, KoreaResearch Laboratory, Dong-A Pharmaceutical Company, Kyunggi-do, KoreaDepartment of Food and Nutrition, Yonsei University, Seoul, KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Hanyang University College of Medicine, Seoul, KoreaDepartment of Biotechnology, Joongbu University, Choongnam, KoreaResearch Laboratory, Dong-A Pharmaceutical Company, Kyunggi-do, KoreaDepartment of Food and Nutrition, Yonsei University, Seoul, KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: N
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Hanyang University College of Medicine, Seoul, KoreaDepartment of Biotechnology, Joongbu University, Choongnam, KoreaResearch Laboratory, Dong-A Pharmaceutical Company, Kyunggi-do, KoreaDepartment of Food and Nutrition, Yonsei University, Seoul, KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Hanyang University College of Medicine, Seoul, KoreaDepartment of Biotechnology, Joongbu University, Choongnam, KoreaResearch Laboratory, Dong-A Pharmaceutical Company, Kyunggi-do, KoreaDepartment of Food and Nutrition, Yonsei University, Seoul, KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: J M
authors.initials: JM
authors.lastname: Kim
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D005419:Flavonoids / Q000378:metabolism / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D015151:Immunoblotting; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018932:Chemokine CCL2; D005419:Flavonoids; D018841:HSP90 Heat-Shock Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D051550:I-kappa B Kinase; C121889:recoflavone