000060423 001__ 60423
000060423 005__ 20240122154813.0
000060423 0247_ $$2doi$$a10.1371/journal.pone.0169303
000060423 0248_ $$2sideral$$a97876
000060423 037__ $$aART-2016-97876
000060423 041__ $$aeng
000060423 100__ $$0(orcid)0000-0002-5797-3909$$aLatorre, E.
000060423 245__ $$aIntestinal serotonin transporter inhibition by toll-like receptor 2 activation. A feedback modulation
000060423 260__ $$c2016
000060423 5060_ $$aAccess copy available to the general public$$fUnrestricted
000060423 5203_ $$aTLR2 is a microbiota recognition receptor that has been described to contribute to intestinal homeostasis and to ameliorate inflammatory intestinal injury. In this context, serotonin (5-HT) has shown to be an essential intestinal physiological neuromodulator that is also involved in intestinal inflammatory diseases. Since the interaction between TLR2 activation and the intestinal serotoninergic system remains non-investigated, our main aim was to analyze the effect of TLR2 on intestinal serotonin transporter (SERT) activity and expression and the intracellular pathways involved. Caco-2/TC7 cells were used to analyze SERT and TLR2 molecular expression and SERT activity by measuring 5-HT uptake. The results showed that apical TLR2 activation inhibits SERT activity in Caco-2/TC7 cells mainly by reducing SERT protein level either in the plasma membrane, after short-term TLR2 activation or in both the plasma membrane and cell lysate, after long-term activation. cAMP/PKA pathway appears to mediate short-term inhibitory effect of TLR2 on SERT; however, p38 MAPK pathway has been shown to be involved in both short- and long-term TLR2 effect. Reciprocally, 5-HT long-term treatment yielded TLR2 down regulation in Caco-2/TC7 cells. Finally, results from in vivo showed an augmented intestinal SERT expression in mice Tlr2-/-, thus confirming our inhibitory effect of TLR2 on intestinal SERT in vitro. The present work infers that TLR2 may act in intestinal pathophysiology, not only by its inherent innate immune role, but also by regulating the intestinal serotoninergic system.
000060423 536__ $$9info:eu-repo/grantAgreement/ES/UZ/UZ2014-BIO-3$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-1-R$$9info:eu-repo/grantAgreement/ES/MICINN-FEDER/BFU2010-18971$$9info:eu-repo/grantAgreement/ES/DGA/B61$$9info:eu-repo/grantAgreement/ES/DGA/B022-13$$9info:eu-repo/grantAgreement/ES/DGA/ARAINF-012-2008
000060423 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000060423 590__ $$a2.806$$b2016
000060423 591__ $$aMULTIDISCIPLINARY SCIENCES$$b15 / 63 = 0.238$$c2016$$dQ1$$eT1
000060423 592__ $$a1.236$$b2016
000060423 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2016$$dQ1
000060423 593__ $$aMedicine (miscellaneous)$$c2016$$dQ1
000060423 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2016$$dQ1
000060423 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000060423 700__ $$0(orcid)0000-0001-5573-6144$$aLayunta, E.$$uUniversidad de Zaragoza
000060423 700__ $$0(orcid)0000-0002-5306-9365$$aGrasa, L.$$uUniversidad de Zaragoza
000060423 700__ $$0(orcid)0000-0001-8584-3979$$aCastro, M.$$uUniversidad de Zaragoza
000060423 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J.$$uUniversidad de Zaragoza
000060423 700__ $$0(orcid)0000-0003-0076-3529$$aGomollón, F.$$uUniversidad de Zaragoza
000060423 700__ $$0(orcid)0000-0002-9935-927X$$aAlcalde, A.I.
000060423 700__ $$0(orcid)0000-0003-4758-3998$$aMesonero, J.E.$$uUniversidad de Zaragoza
000060423 7102_ $$11005$$2410$$aUniversidad de Zaragoza$$bDpto. Farmacología y Fisiolog.$$cÁrea Fisiología
000060423 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000060423 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000060423 773__ $$g11, 12 (2016), [20 pp.]$$pPLoS One$$tPLoS ONE$$x1932-6203
000060423 8564_ $$s2696527$$uhttps://zaguan.unizar.es/record/60423/files/texto_completo.pdf$$yVersión publicada
000060423 8564_ $$s101616$$uhttps://zaguan.unizar.es/record/60423/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
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000060423 951__ $$a2024-01-22-15:31:46
000060423 980__ $$aARTICLE