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H<jats:sub>2<\/jats:sub>S production in colon is yielded by cystathionine \u03b2\u2010synthase (CBS) and cystathionine \u03b3\u2010lyase (CSE) enzymes and sulfate\u2010reducing bacteria (SRB). Toll\u2010like receptors (TLRs) recognize intestinal microbiota. The aim of this work was to evaluate the influence of TLR2 and TLR4 on the endogenous and SRB\u2010mediated synthesis of H<jats:sub>2<\/jats:sub>S and its consequences on the colonic motility of mouse.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Muscle contractility studies were performed in colon from WT, <jats:italic>Tlr2<\/jats:italic><jats:sup>\u2010\/\u2010<\/jats:sup>, and <jats:italic>Tlr4<\/jats:italic><jats:sup>\u2010\/\u2010<\/jats:sup> mice. The mRNA levels of TLR2, TLR4, CBS, CSE, and SRB were measured by real\u2010time PCR. Free sulfide levels in colon and feces were determined by colorimetric assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NaHS and GYY4137, donors of H<jats:sub>2<\/jats:sub>S, reduced the contractility of colon. Aminooxyacetic acid (AOAA), inhibitor of CBS, and D\u2010L propargylglycine (PAG), inhibitor of CSE, increased the contractility of colon. <jats:italic>In vivo<\/jats:italic> treatment with NaHS or GYY4137 inhibited the spontaneous contractions and upregulated TLR2 expression. The <jats:italic>in vivo<\/jats:italic> activation of TLR4 with lipopolysaccharide increased the contractile response to PAG, mRNA levels of CSE, and the free sulfide levels of H<jats:sub>2<\/jats:sub>S in colon. In <jats:italic>Tlr2<\/jats:italic><jats:sup>\u2010\/\u2010<\/jats:sup> and <jats:italic>Tlr4<\/jats:italic><jats:sup>\u2010\/\u2010<\/jats:sup>\u00a0mice, the contractions induced by AOAA and PAG and mRNA levels of CBS and CSE were lower with respect to WT mice. Deficiency of TLR2 or TLR4 provokes alterations in free sulfide levels and SRB of colon.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Inferences<\/jats:title><jats:p>Our study demonstrates interaction between TLR2 and TLR4 and the sulfide system in the regulation of colonic motility and contributes to the pathophysiology knowledge of intestinal motility disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13648","type":"journal-article","created":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T14:02:57Z","timestamp":1558620177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["TLR2 and TLR4 interact with sulfide system in the modulation of mouse colonic motility"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5306-9365","authenticated-orcid":false,"given":"Laura","family":"Grasa","sequence":"first","affiliation":[{"name":"Departamento de Farmacolog\u00eda y 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