TLR2 and TLR4 interact with sulfide system in the modulation of mouse colonic motility
| Autor: | Raquel Forcén, Sofia Robles, Elena Layunta, Laura Grasa, Eva Latorre, José E. Mesonero, Leticia Abecia, Ainize Peña-Cearra |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Lipopolysaccharide Colon Physiology Morpholines Endogeny Pharmacology Contractility Mice 03 medical and health sciences chemistry.chemical_compound Organ Culture Techniques 0302 clinical medicine In vivo Animals Hydrogen Sulfide Receptor Mice Knockout Dose-Response Relationship Drug biology Endocrine and Autonomic Systems Gastroenterology Organothiophosphorus Compounds Cystathionine beta synthase Aminooxyacetic acid Toll-Like Receptor 2 Mice Inbred C57BL Toll-Like Receptor 4 030104 developmental biology chemistry 030220 oncology & carcinogenesis TLR4 biology.protein Gastrointestinal Motility Muscle Contraction |
| Zdroj: | Zaguán. Repositorio Digital de la Universidad de Zaragoza instname |
| Popis: | Background H2S is a neuromodulator that may inhibit intestinal motility. H2S production in colon is yielded by cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) enzymes and sulfate-reducing bacteria (SRB). Toll-like receptors (TLRs) recognize intestinal microbiota. The aim of this work was to evaluate the influence of TLR2 and TLR4 on the endogenous and SRB-mediated synthesis of H2S and its consequences on the colonic motility of mouse. Methods Muscle contractility studies were performed in colon from WT, Tlr2(-/-), and Tlr4(-/-) mice. The mRNA levels of TLR2, TLR4, CBS, CSE, and SRB were measured by real-time PCR. Free sulfide levels in colon and feces were determined by colorimetric assays. Results NaHS and GYY4137, donors of H2S, reduced the contractility of colon. Aminooxyacetic acid (AOAA), inhibitor of CBS, and D-L propargylglycine (PAG), inhibitor of CSE, increased the contractility of colon. In vivo treatment with NaHS or GYY4137 inhibited the spontaneous contractions and upregulated TLR2 expression. The in vivo activation of TLR4 with lipopolysaccharide increased the contractile response to PAG, mRNA levels of CSE, and the free sulfide levels of H2S in colon. In Tlr2(-/-) and Tlr4(-/-) mice, 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. Conclusions and Inferences 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. |
| Databáze: | OpenAIRE |
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