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Methods to Study Epithelial Transport Protein Function and Expression in Native Intestine and Caco-2 Cells Grown in 3D
Published on: March 16, 2017
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Intestinal serotonergic system is modulated by Toll-like receptor 9
Elena Layunta1,2, Eva Latorre3,4,5, Laura Grasa2,6,7
1Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
Journal of Physiology and Biochemistry
|June 7, 2022
Summary
Toll-like receptor 9 (TLR9) activation inhibits serotonin transporter activity and expression in the intestine. This interaction suggests TLR9 plays a role in maintaining intestinal homeostasis by modulating the serotonergic system.
Area of Science:
- Gastroenterology
- Immunology
- Neuroscience
Background:
- The intestinal serotonergic system regulates gut homeostasis, but its precise control mechanisms remain incompletely understood.
- Toll-like receptor 9 (TLR9) is an innate immune receptor crucial for detecting intestinal pathogens and maintaining gut integrity.
- The specific role of TLR9 in the intestinal serotonergic system is largely unexplored.
Purpose of the Study:
- To investigate the regulatory relationship between Toll-like receptor 9 (TLR9) and the intestinal serotonergic system.
- To elucidate the molecular mechanisms underlying TLR9-serotonin interactions in the gut.
Main Methods:
- Utilized the Caco-2/TC7 cell line and Tlr9 knockout (Tlr9-/-) mice models.
- Assessed serotonin uptake, and analyzed the molecular expression of serotonergic components via Western blot and real-time PCR.
Main Results:
- TLR9 activation was found to inhibit serotonin transporter (SERT) activity and expression, involving p38/MAPK and ERK/MAPK signaling pathways.
- Reciprocally, serotonin was observed to increase TLR9 expression.
- Significant alterations in SERT, serotonin receptors, and serotonin-producing enzymes were detected in the intestinal tracts of Tlr9-/- mice.
Conclusions:
- TLR9 activation modulates the intestinal serotonergic system by inhibiting serotonin transporter function and expression.
- A reciprocal regulatory loop exists between TLR9 and serotonin in the intestine.
- TLR9 contributes to the maintenance of intestinal homeostasis through its interaction with the serotonergic system.
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