Caffeic acid phenethyl ester modulatesHelicobacter pylori‐induced nuclear factor‐kappa B and activator protein‐1 expression in gastric epithelial cells

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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 onHelicobacter pylori‐induced NF‐κB and AP‐1 in the gastric epithelial cell line AGS. Electrophoretic mobility shift assay was used to measure NF‐κB‐ and AP‐1‐DNA binding activity. Western blotting was used to detect IκB‐αand COX‐2 expression in AGS cells cocultured withH. pylori. The antiproliferative effect of CAPE was measured by MTT assay. Our results showed that caffeic phenethyl ester inhibitsH. pylori‐induced NF‐κB and AP‐1 DNA‐binding activity in a dose (0.1–25 μg ml−1∼0.35–88 μM) and time‐ (15–240 min) dependent manner in AGS cells. Maximum inhibition by CAPE was observed at concentrations of 25 μg ml−1(∼88 μM) CAPE preventedH. pylori‐ and cytokine‐induced degradation of IκB‐αprotein. Pretreatment of AGS cells with CAPE also blocked cytokine‐ and mitogen‐induced NF‐κB and AP‐1 expression. Furthermore, CAPE suppressedH. pylori‐induced cell proliferation and production of the cytokines TNF‐αand IL‐8. In addition, CAPE blockedH. pylori‐induced COX‐2 expression. The inhibition of such transcription by CAPE could result in suppression of many genes duringH. pylori‐induced inflammation, and also provide new insights into the anti‐cancer and anti‐inflammatory properties of CAPE. British Journal of Pharmacology(2005)146, 1139–1147. doi:10.1038/sj.bjp.0706421

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