Abstract
TLR2 is a microbiota recognition receptor that has been described to contribute to intestinal homeostasis and to ameliorate inflammatory intestinal injury. In this context, serotonin (5-HT) has shown to be an essential intestinal physiological neuromodulator that is also involved in intestinal inflammatory diseases. Since the interaction between TLR2 activation and the intestinal serotoninergic system remains non-investigated, our main aim was to analyze the effect of TLR2 on intestinal serotonin transporter (SERT) activity and expression and the intracellular pathways involved. Caco-2/TC7 cells were used to analyze SERT and TLR2 molecular expression and SERT activity by measuring 5-HT uptake. The results showed that apical TLR2 activation inhibits SERT activity in Caco-2/TC7 cells mainly by reducing SERT protein level either in the plasma membrane, after short-term TLR2 activation or in both the plasma membrane and cell lysate, after long-term activation. cAMP/PKA pathway appears to mediate short-term inhibitory effect of TLR2 on SERT; however, p38 MAPK pathway has been shown to be involved in both short- and long-term TLR2 effect. Reciprocally, 5-HT long-term treatment yielded TLR2 down regulation in Caco-2/TC7 cells. Finally, results from in vivo showed an augmented intestinal SERT expression in mice Tlr2-/-, thus confirming our inhibitory effect of TLR2 on intestinal SERT in vitro. The present work infers that TLR2 may act in intestinal pathophysiology, not only by its inherent innate immune role, but also by regulating the intestinal serotoninergic system.
Highlights
Intestinal epithelium contributes to intestinal physiology and homeostasis, by acting as a physical barrier between the body and the microorganisms present in the lumen, and by carrying out an active participation in the mucosal immune response [1, 2]
In order to analyze the effect of TLR2 activation on serotonin transporter (SERT) activity, 5-HT uptake in Caco-2/TC7 cells was measured in cells treated with Pam3CSK4 (TLR2/1 ligand) or Pam2CSK4 (TLR2/6 ligand) at different concentrations and periods of treatment (30 min and 1 day)
The results have shown that the treatment of cells with either TLR2/1 or TLR2/6 ligands inhibited 5-HT uptake by mainly affecting Vmax (SERT capacity) at both short (30 minutes) and long-term (1 day)
Summary
Intestinal epithelium contributes to intestinal physiology and homeostasis, by acting as a physical barrier between the body and the microorganisms present in the lumen (microbiota), and by carrying out an active participation in the mucosal immune response [1, 2]. Immunological activity mediated by TLRs protects and maintains the integrity of the mucosal barrier, contributing to the homeostasis and intestinal physiology. In this context, recent results have demonstrated that TLR2 may play an important role in intestinal homeostasis, and variants in the TLR1/2/6 genes have been associated with different phenotypes of IBDs [6]. Considering its activities on epithelial barrier function, TLR2 signaling has been postulated to ameliorate intestinal injury induced by chronic inflammatory processes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
