000075532 001__ 75532
000075532 005__ 20240122154813.0
000075532 0247_ $$2doi$$a10.1002/jcp.26229
000075532 0248_ $$2sideral$$a102261
000075532 037__ $$aART-2018-102261
000075532 041__ $$aeng
000075532 100__ $$0(orcid)0000-0001-5573-6144$$aLayunta, E.
000075532 245__ $$aNOD1 downregulates intestinal serotonin transporter and interacts with other pattern recognition receptors
000075532 260__ $$c2018
000075532 5060_ $$aAccess copy available to the general public$$fUnrestricted
000075532 5203_ $$aSerotonin (5-HT) is an essential gastrointestinal modulator whose effects regulate the intestinal physiology. 5-HT effects depend on extracellular 5-HT bioavailability, which is controlled by the serotonin transporter (SERT) expressed in both the apical and basolateral membranes of enterocytes. SERT is a critical target for regulating 5-HT levels and consequently, modulating the intestinal physiology. The deregulation of innate immune receptors has been extensively studied in inflammatory bowel diseases (IBD), where an exacerbated defense response to commensal microbiota is observed. Interestingly, many innate immune receptors seem to affect the serotonergic system, demonstrating a new way in which microbiota could modulate the intestinal physiology. Therefore, our aim was to analyze the effects of NOD1 activation on SERT function, as well as NOD1's interaction with other immune receptors such as TLR2 and TLR4. Our results showed that NOD1 activation inhibits SERT activity and expression in Caco-2/TC7 cells through the extracellular signal-regulated kinase (ERK) signaling pathway. A negative feedback between 5-HT and NOD1 expression was also described. The results showed that TLR2 and TLR4 activation seems to regulate NOD1 expression in Caco-2/TC7 cells. To assess the extend of cross-talk between NOD1 and TLRs, NOD1 expression was measured in the intestinal tract (ileum and colon) of wild type mice and mice with individual knockouts of TLR2, and TLR4 as well as double knockout TLR2/TLR4 mice. Hence, we demonstrate that NOD1 acts on the serotonergic system decreasing SERT activity and molecular expression. Additionally, NOD1 expression seems to be modulated by 5-HT and other immune receptors as TLR2 and TLR4. This study could clarify the relation between both the intestinal serotonergic system and innate immune system, and their implications in intestinal inflammation.
000075532 536__ $$9info:eu-repo/grantAgreement/ES/DGA/ARAINF-012-2008$$9info:eu-repo/grantAgreement/ES/DGA/B022-13$$9info:eu-repo/grantAgreement/ES/DGA/B61$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-1-R
000075532 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000075532 590__ $$a4.522$$b2018
000075532 591__ $$aPHYSIOLOGY$$b11 / 81 = 0.136$$c2018$$dQ1$$eT1
000075532 591__ $$aCELL BIOLOGY$$b62 / 191 = 0.325$$c2018$$dQ2$$eT1
000075532 592__ $$a1.445$$b2018
000075532 593__ $$aCell Biology$$c2018$$dQ1
000075532 593__ $$aPhysiology$$c2018$$dQ1
000075532 593__ $$aClinical Biochemistry$$c2018$$dQ1
000075532 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/submittedVersion
000075532 700__ $$0(orcid)0000-0002-5797-3909$$aLatorre, E.$$uUniversidad de Zaragoza
000075532 700__ $$aForcen, R,
000075532 700__ $$0(orcid)0000-0002-5306-9365$$aGrasa, L.$$uUniversidad de Zaragoza
000075532 700__ $$0(orcid)0000-0002-7412-2073$$aPlaza, M. A.$$uUniversidad de Zaragoza
000075532 700__ $$0(orcid)0000-0002-9730-2210$$aArias, M.$$uUniversidad de Zaragoza
000075532 700__ $$0(orcid)0000-0002-9935-927X$$aAlcalde, A. I.
000075532 700__ $$0(orcid)0000-0003-4758-3998$$aMesonero, J. E.$$uUniversidad de Zaragoza
000075532 7102_ $$11005$$2410$$aUniversidad de Zaragoza$$bDpto. Farmacología y Fisiolog.$$cÁrea Fisiología
000075532 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000075532 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000075532 773__ $$g233, 5 (2018), 4183-4193$$pJ. cell. physiol.$$tJOURNAL OF CELLULAR PHYSIOLOGY$$x0021-9541
000075532 8564_ $$s696128$$uhttps://zaguan.unizar.es/record/75532/files/texto_completo.pdf$$yPreprint
000075532 8564_ $$s68732$$uhttps://zaguan.unizar.es/record/75532/files/texto_completo.jpg?subformat=icon$$xicon$$yPreprint
000075532 909CO $$ooai:zaguan.unizar.es:75532$$particulos$$pdriver
000075532 951__ $$a2024-01-22-15:30:53
000075532 980__ $$aARTICLE