title: IL-10 modulates serotonin transporter activity and molecular expression in intestinal epithelial cells.
abstract: Serotonin is a neuromodulator mainly synthesized by intestinal enterochromaffin cells that regulate overall intestinal physiology. The serotonin transporter (SERT) determines the final serotonin availability and has been described as altered in inflammatory bowel diseases. IL-10 is an anti-inflammatory cytokine that is involved in intestinal inflammatory processes and also contributes to intestinal mucosa homeostasis. The regulation of SERT by pro-inflammatory factors is well known; however, the effect of IL-10 on the intestinal serotoninergic system mediated by SERT remains unknown. Therefore, the aim of the present study is to determine whether IL-10 affects SERT activity and expression in enterocyte-like Caco-2 cells. Treatment with IL-10 was assessed and SERT activity was determined by 5-HT uptake. SERT mRNA and protein expression was analyzed using quantitative RT-PCR and western blotting. The results showed that IL-10 induced a dual effect on SERT after 6h of treatment. On one hand, IL-10, at a low concentration, inhibited SERT activity, and this effect might be explained by a non-competitive inhibition of SERT. On the other hand, IL-10, at a high concentration, increased SERT activity and molecular expression in the membrane of the cells. This effect was mediated by the IL-10 receptor and triggered by the PI3K intracellular pathway. Our results demonstrate that IL-10 modulates SERT activity and expression, depending on its extracellular conditions. This study may contribute to understand serotoninergic responses in intestinal pathophysiology.
authors: Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, Universidad de Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain.
authors: Eva
authors: E
authors: Latorre
authors: Carmen
authors: C
authors: Mendoza
authors: Nyurky
authors: N
authors: Matheus
authors: Marta
authors: M
authors: Castro
authors: Laura
authors: L
authors: Grasa
authors: José E
authors: JE
authors: Mesonero
authors: Ana I
authors: AI
authors: Alcalde
mesh_terms: D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D007422:Intestines / Q000166:cytology*; D007700:Kinetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
chemical_list: D021122:Protein Subunits; D012333:RNA, Messenger; D053701:Receptors, Interleukin-10; D050486:Serotonin Plasma Membrane Transport Proteins; D016753:Interleukin-10; D012701:Serotonin; D019869:Phosphatidylinositol 3-Kinases