title: Caffeic acid phenethyl ester modulates Helicobacter pylori-induced nuclear factor-kappa B and activator protein-1 expression in gastric epithelial cells.
abstract: Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives (honeybee resin), has anti-inflammatory, anti-carcinogenic and anti-bacterial properties. This study was designed to investigate the anti-inflammatory effects of CAPE on Helicobacter pylori-induced NF-kappaB and AP-1 in the gastric epithelial cell line AGS. Electrophoretic mobility shift assay was used to measure NF-kappaB- and AP-1-DNA binding activity. Western blotting was used to detect IkappaB-alpha and COX-2 expression in AGS cells cocultured with H. pylori. The antiproliferative effect of CAPE was measured by MTT assay. Our results showed that caffeic phenethyl ester inhibits H. pylori-induced NF-kappaB and AP-1 DNA-binding activity in a dose (0.1-25 microg ml(-1) approximately 0.35-88 microM) and time- (15-240 min) dependent manner in AGS cells. Maximum inhibition by CAPE was observed at concentrations of 25 microg ml(-1) ( approximately 88 microM) CAPE prevented H. pylori- and cytokine-induced degradation of IkappaB-alpha protein. Pretreatment of AGS cells with CAPE also blocked cytokine- and mitogen-induced NF-kappaB and AP-1 expression. Furthermore, CAPE suppressed H. pylori-induced cell proliferation and production of the cytokines TNF-alpha and IL-8. In addition, CAPE blocked H. pylori-induced COX-2 expression. The inhibition of such transcription by CAPE could result in suppression of many genes during H. pylori-induced inflammation, and also provide new insights into the anti-cancer and anti-inflammatory properties of CAPE.
authors.affiliation: Department of Clinical Medicine, Dublin Molecular Medicine Centre and Trinity Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland. abdellmm@tcd.ie
authors.forename: Mohamed M M
authors.initials: MM
authors.lastname: Abdel-Latif
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Windle
authors.forename: Basma S El
authors.initials: BS
authors.lastname: Homasany
authors.forename: Kamal
authors.initials: K
authors.lastname: Sabra
authors.forename: Dermot
authors.initials: D
authors.lastname: Kelleher
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000382:microbiology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000382:microbiology; D016481:Helicobacter Infections / Q000378:metabolism* / Q000517:prevention & control; D016480:Helicobacter pylori; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D002109:Caffeic Acids; D016207:Cytokines; D020672:I-kappa B Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol