Adiponectin Modulates DCA-Induced Inflammation via the ROS/NF-Kappa B Signaling Pathway in Esophageal Adenocarcinoma Cells

Background Deoxycholic acid (DCA) promotes the development and progression of esophageal adenocarcinoma (EAC) by inducing inflammation. Adiponectin is reported to have anti-inflammatory and anti-tumor effects. This study investigated the effects of two types of adiponectin, full-length adiponectin (f-Ad) and globular adiponectin (g-Ad), on DCA-induced inflammation, and investigated the involvement of the reactive oxygen species (ROS)/NF-kappa B signaling pathway in inflammation in EAC. OE19 cells were treated with DCA (50-300 mu M) and/or f-Ad/g-Ad (10.0 mu g/ml) or N-acetylcysteine (NAC). The viability of cells exposed to DCA was measured by use of the MTT assay. mRNA and protein levels of the inflammatory factors were examined by real-time PCR and ELISA. Intra-cellular ROS levels were determined by use of flow cytometry. Protein levels of total and p-NF-kappa B p65 were measured by western blot. DCA induced dose and time-dependent cytotoxicity. mRNA and protein expression of TNF-alpha, IL-8, and IL-6 in cells treated with DCA alone were up-regulated, and intra-cellular ROS and p-NF-kappa B p65 protein levels were also increased. g-Ad promoted inflammatory factor production, ROS levels, and p-NF-kappa B p65 protein expression whereas f-Ad had a suppressive effect. When combined with DCA, g-Ad enhanced the pro-inflammatory effect of DCA whereas f-Ad, similar to NAC, suppressed the effect. DCA has a pro-inflammatory effect in EAC. f-Ad has an anti-inflammatory effect whereas g-Ad seems to have a pro-inflammatory effect in an ROS/NF-kappa B p65-dependent manner. This indicates that f-Ad could be a potential anti-inflammatory reagent for cancer therapy.