The serotonin reuptake transporter is reduced in the epithelium of active Crohn's disease and ulcerative colitis.

In this study we show a potent and significant downregulation of the dominant serotonin reuptake transporter (SERT) mRNA (SLC6A4) in active CD ileitis, CD colitis and UC colitis, compared to healthy controls. The mRNA of the rate-limiting enzyme in serotonin synthesis, tryptophan hydroxylase 1 was unregulated. Immunohistochemistry showed expression of SERT protein in both the epithelium and the lamina propria and localised the downregulation to the epithelial monolayer. Laser capture microdissection followed by RNA sequencing confirmed downregulation of SLC6A4 in the epithelial monolayer during intestinal inflammation. Patient-derived colon epithelial cell lines (colonoids) incubated with the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) reduced SERT expression. In summary, these results show that intestinal inflammation potently reduces the expression of SERT in both CD and UC, and that TNFα alone is sufficient to induce a similar reduction in colonoids. The reduced serotonin reuptake capacity may contribute to the increased interstitial serotonin level associated with intestinal inflammation. PMID: 32967429 [PubMed - as supplied by publisher]
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research