Differential effects of indole and serotonin on TNF‐α‐induced inflammatory response in HT‐29 colon epithelial cells

Inflammatory bowel disease (IBD) is characterized by an excessive release of several proinflammatory cytokines which results consequently in an increased inflammatory response. Serotonin (5‐Hydroxytrytamine, 5‐HT) is a major gastrointestinal paracrine hormone and enteric neurotransmitter. Studies on human IBD and experimental animal models have shown increased 5‐HT level in the inflamed gut. In this study, we investigated the effects of serotonin on the initial event of intestinal inflammation in vitro by measuring the degree of monocyte adhesion to colonic epithelial cells. Indole, 3,3′‐Methylene‐bisindole, and 3‐Indolyl‐acetonitrile but not 5‐HT significantly suppressed tumor necrosis factor‐alpha (TNF‐α)‐induced adhesion of monocyte to HT29 cells. Rather, similar to TNF‐α, 5‐HT induced monocyte‐HT‐29 adhesion in a concentration‐dependent manner, which was reversed by the treatment with RS39604, a selective 5‐HT 4 receptor antagonist. No additive effect was seen in case of co‐treatment of the cells with serotonin and TNF‐α. In addition, serotonin‐induced inflammatory response subsided well by the treatment with phloretin (50 μM), a dietary polyphenol, compared to TNF‐α‐induced inflammation. These results indicate that serotonin acts as a proinflammatory factor working in a different mechanism from TNF‐α.