75532 20240122154813.0 doi 10.1002/jcp.26229 sideral 102261 ART-2018-102261 eng Layunta, E. (orcid)0000-0001-5573-6144 NOD1 downregulates intestinal serotonin transporter and interacts with other pattern recognition receptors 2018 Access copy available to the general public Unrestricted Serotonin (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. info:eu-repo/grantAgreement/ES/DGA/ARAINF-012-2008 info:eu-repo/grantAgreement/ES/DGA/B022-13 info:eu-repo/grantAgreement/ES/DGA/B61 info:eu-repo/grantAgreement/ES/MINECO/SAF2014-54763-C2-1-R info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 4.522 2018 PHYSIOLOGY 11 / 81 = 0.136 2018 Q1 T1 CELL BIOLOGY 62 / 191 = 0.325 2018 Q2 T1 1.445 2018 Cell Biology 2018 Q1 Physiology 2018 Q1 Clinical Biochemistry 2018 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/submittedVersion Latorre, E. Universidad de Zaragoza (orcid)0000-0002-5797-3909 Forcen, R, Grasa, L. Universidad de Zaragoza (orcid)0000-0002-5306-9365 Plaza, M. A. Universidad de Zaragoza (orcid)0000-0002-7412-2073 Arias, M. Universidad de Zaragoza (orcid)0000-0002-9730-2210 Alcalde, A. I. (orcid)0000-0002-9935-927X Mesonero, J. E. Universidad de Zaragoza (orcid)0000-0003-4758-3998 1005 410 Universidad de Zaragoza Dpto. Farmacología y Fisiolog. Área Fisiología 1008 566 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Inmunología 1002 050 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Biología Celular 233, 5 (2018), 4183-4193 J. cell. physiol. JOURNAL OF CELLULAR PHYSIOLOGY 0021-9541 696128 http://zaguan.unizar.es/record/75532/files/texto_completo.pdf Preprint 68732 http://zaguan.unizar.es/record/75532/files/texto_completo.jpg?subformat=icon icon Preprint oai:zaguan.unizar.es:75532 articulos driver 2024-01-22-15:30:53 ARTICLE