000071094 001__ 71094
000071094 005__ 20240122154813.0
000071094 0247_ $$2doi$$a10.1159/000490218.
000071094 0248_ $$2sideral$$a106704
000071094 037__ $$aART-2018-106704
000071094 041__ $$aeng
000071094 100__ $$0(orcid)0000-0001-5573-6144$$aLayunta, E,
000071094 245__ $$aNOD2 Modulates Serotonin Transporter and Interacts with TLR2 and TLR4 in Intestinal Epithelial Cells
000071094 260__ $$c2018
000071094 5060_ $$aAccess copy available to the general public$$fUnrestricted
000071094 5203_ $$aBackground/Aims: Serotonin (5-HT) is a chief modulator of intestinal activity. The effects of 5-HT depend on its extracellular availability, which is mainly controlled by serotonin transporter (SERT), expressed in enterocytes. On the other hand, innate immunity, mediated by Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD)-like receptors (NLRs), is known to control intestinal microbiota and maintain intestinal homeostasis. The dysregulation of the intestinal serotonergic system and innate immunity has been observed in in ammatory bowel diseases (IBD), the incidence of which has severely increased all over the world. The aim of the present study, therefore, was to analyze the effect of NOD2 on intestinal SERT activity and expression, as well as to study the crosstalk of NOD2 with TLR2 and TLR4. 
Methods: Intestinal epithelial cell line Caco-2/TC7 was used to analyze SERT activity and SERT, NOD2, TLR2 and TLR4 molecular expression by real-time PCR and western blotting. Moreover, intestinal tract (ileum and colon) from mice de cient in TLR2, TLR4 or TLR2/4 receptors was used to test the interdependence of NOD2 with these TLR receptors. Results: NOD2 activation inhibits SERT activity in Caco-2/TC7 cells, mainly due to the decrement of SERT molecular expression, with RIP2/RICK being the intracellular pathway involved in this effect. This inhibitory effect on SERT would yield an increment of extracellular 5-HT availability. In this sense, 5-HT strongly inhibits NOD2 expression. In addition, NOD2 showed greater interdependence with TLR2 than with TLR4. Indeed, NOD2 expression signi cantly increased in both cells treated with TLR2 agonists and the intestinal tract of Tlr2-/- mice. 
Conclusions: It may be inferred from our data that NOD2 could play a role in intestinal pathophysiology not only through its inherent innate immune role but also due to its interaction with other receptors as TLR2 and the modulation of the intestinal serotonergic system decreasing SERT activity and expression.
000071094 536__ $$9info:eu-repo/grantAgreement/ES/DGA/ARAINF-012-2008$$9info:eu-repo/grantAgreement/ES/DGA/B022-13$$9info:eu-repo/grantAgreement/ES/DGA/B61$$9info:eu-repo/grantAgreement/ES/MICINN-FEDER/BFU2010-18971
000071094 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000071094 592__ $$a1.292$$b2018
000071094 593__ $$aPhysiology$$c2018$$dQ2
000071094 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000071094 700__ $$0(orcid)0000-0002-5797-3909$$aLatorre, E,$$uUniversidad de Zaragoza
000071094 700__ $$aForcén, R,
000071094 700__ $$0(orcid)0000-0002-5306-9365$$aGrasa, L,$$uUniversidad de Zaragoza
000071094 700__ $$0(orcid)0000-0001-8584-3979$$aCastro, M,$$uUniversidad de Zaragoza
000071094 700__ $$0(orcid)0000-0002-9730-2210$$aArias, M.A,$$uUniversidad de Zaragoza
000071094 700__ $$0(orcid)0000-0002-9935-927X$$aAlcalde, A.I,
000071094 700__ $$0(orcid)0000-0003-4758-3998$$aMesonero, J.E.$$uUniversidad de Zaragoza
000071094 7102_ $$11005$$2410$$aUniversidad de Zaragoza$$bDpto. Farmacología y Fisiolog.$$cÁrea Fisiología
000071094 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000071094 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000071094 773__ $$g47, 3 (2018), 1217-1229$$pCell. physiol. biochem.$$tCellular physiology and biochemistry$$x1015-8987
000071094 8564_ $$s1609015$$uhttps://zaguan.unizar.es/record/71094/files/texto_completo.pdf$$yVersión publicada
000071094 8564_ $$s101691$$uhttps://zaguan.unizar.es/record/71094/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000071094 909CO $$ooai:zaguan.unizar.es:71094$$particulos$$pdriver
000071094 951__ $$a2024-01-22-15:32:01
000071094 980__ $$aARTICLE