IL-10 modulates serotonin transporter activity and molecular expression in intestinal epithelial cells

► Serotonin and IL-10 are involved in intestinal homeostasis and pathophysiology. ► Serotonin transporter regulation by IL-10 was studied in Caco-2 cells. ► IL-10 at a low concentration inhibited SERT activity. ► IL-10 at a high concentration increased SERT activity and membrane expression. ► IL-10...

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Bibliographic Details
Published in:Cytokine (Philadelphia, Pa.) Pa.), 2013-03, Vol.61 (3), p.778-784
Main Authors: Latorre, Eva, Mendoza, Carmen, Matheus, Nyurky, Castro, Marta, Grasa, Laura, Mesonero, José E., Alcalde, Ana I.
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
5-HT
Biological Transport - drug effects
Biological Transport - genetics
Caco-2 Cells
Epithelial cells
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Gene expression
Gene Expression Regulation - drug effects
Homeostasis
Humans
IL-10
Inflammatory bowel diseases
Interleukin 10
Interleukin-10 - pharmacology
Intestine
Intestines - cytology
Kinetics
mRNA
Mucosa
Neuromodulation
Phosphatidylinositol 3-Kinases - metabolism
Polymerase chain reaction
Protein Subunits - genetics
Protein Subunits - metabolism
Receptors, Interleukin-10 - genetics
Receptors, Interleukin-10 - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Serotonin
Serotonin - metabolism
Serotonin Plasma Membrane Transport Proteins - genetics
Serotonin Plasma Membrane Transport Proteins - metabolism
Serotonin transporter
Signal Transduction - drug effects
Signal Transduction - genetics
Time Factors
Western blotting
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Summary:► Serotonin and IL-10 are involved in intestinal homeostasis and pathophysiology. ► Serotonin transporter regulation by IL-10 was studied in Caco-2 cells. ► IL-10 at a low concentration inhibited SERT activity. ► IL-10 at a high concentration increased SERT activity and membrane expression. ► IL-10 modulates SERT and serotonin availability depending on intestinal conditions. 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.
ISSN:1043-4666
1096-0023
DOI:10.1016/j.cyto.2013.01.012