scholarly journals NOD2 Modulates Serotonin Transporter and Interacts with TLR2 and TLR4 in Intestinal Epithelial Cells

2018 ◽  
Vol 47 (3) ◽  
pp. 1217-1229 ◽  
Author(s):  
Elena Layunta ◽  
Eva Latorre ◽  
Raquel Forcén ◽  
Laura Grasa ◽  
Marta Castro ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Serotonin Transporter ◽  
Intestinal Tract ◽  
Inhibitory Effect ◽  
Serotonergic System ◽  
Epithelial Cell Line ◽  
Intestinal Epithelial ◽  
Bowel Diseases ◽  
Molecular Expression ◽  
Sert Activity

Background/Aims: Serotonin (5-HT) is a chief modulator of intestinal activity. The effects of 5-HT depend on its extracellular availability, which is mainly controlled by serotonin transporter (SERT), expressed in enterocytes. On the other hand, innate immunity, mediated by Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD)-like receptors (NLRs), is known to control intestinal microbiota and maintain intestinal homeostasis. The dysregulation of the intestinal serotonergic system and innate immunity has been observed in inflammatory bowel diseases (IBD), the incidence of which has severely increased all over the world. The aim of the present study, therefore, was to analyze the effect of NOD2 on intestinal SERT activity and expression, as well as to study the crosstalk of NOD2 with TLR2 and TLR4. Methods: Intestinal epithelial cell line Caco-2/TC7 was used to analyze SERT activity and SERT, NOD2, TLR2 and TLR4 molecular expression by real-time PCR and western blotting. Moreover, intestinal tract (ileum and colon) from mice deficient in TLR2, TLR4 or TLR2/4 receptors was used to test the interdependence of NOD2 with these TLR receptors. Results: NOD2 activation inhibits SERT activity in Caco-2/TC7 cells, mainly due to the decrement of SERT molecular expression, with RIP2/RICK being the intracellular pathway involved in this effect. This inhibitory effect on SERT would yield an increment of extracellular 5-HT availability. In this sense, 5-HT strongly inhibits NOD2 expression. In addition, NOD2 showed greater interdependence with TLR2 than with TLR4. Indeed, NOD2 expression significantly increased in both cells treated with TLR2 agonists and the intestinal tract of Tlr2-/- mice. Conclusions: It may be inferred from our data that NOD2 could play a role in intestinal pathophysiology not only through its inherent innate immune role but also due to its interaction with other receptors as TLR2 and the modulation of the intestinal serotonergic system decreasing SERT activity and expression.

scholarly journals Hepatocyte nuclear factor-4α regulates expression of the serotonin transporter in intestinal epithelial cells

2020 ◽  
Vol 318 (6) ◽  
pp. C1294-C1304
Author(s):  
Nathaniel W. Holton ◽  
Megha Singhal ◽  
Anoop Kumar ◽  
Alexander L. Ticho ◽  
Christopher R. Manzella ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Site Directed Mutagenesis ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Intestinal Epithelial ◽  
Start Site ◽  
Cellular Functions ◽  
Mrna Variant ◽  
Translation Start ◽  
Bowel Diseases

The serotonin transporter (SERT) functions to regulate the availability of serotonin (5-HT) in the brain and intestine. An intestine-specific mRNA variant arising from a unique transcription start site and alternative promoter in the SERT gene has been identified (iSERT; spanning exon 1C). A decrease in SERT is implicated in several gut disorders, including inflammatory bowel diseases (IBD). However, little is known about mechanisms regulating the iSERT variant, and a clearer understanding is warranted for targeting SERT for the treatment of gut disorders. The current studies examined the expression of iSERT across different human intestinal regions and investigated its regulation by HNF4α (hepatic nuclear factor-4α), a transcription factor important for diverse cellular functions. iSERT mRNA abundance was highest in the human ileum and Caco-2 cell line. iSERT mRNA expression was downregulated by loss of HNF4α (but not HNF1α, HNF1β, or FOXA1) in Caco-2 cells. Overexpression of HNF4α increased iSERT mRNA concomitant with an increase in SERT protein. Progressive promoter deletion and site-directed mutagenesis revealed that the HNF4α response element spans nucleotides −1,163 to −1150 relative to the translation start site. SERT mRNA levels in the intestine were drastically reduced in the intestine-specific HNF4α-knockout mice relative to HNF4αFL/FL mice. Both HNF4α and SERT mRNA levels were also downregulated in mouse model of ileitis (SAMP) compared with AKR control mice. These results establish the transcriptional regulation of iSERT at the gut-specific internal promoter (hSERTp2) and have identified HNF4α as a critical modulator of basal SERT expression in the intestine.

IL-10 modulates serotonin transporter activity and molecular expression in intestinal epithelial cells

Cytokine ◽  
2013 ◽  
Vol 61 (3) ◽  
pp. 778-784 ◽  
Author(s):  
Eva Latorre ◽  
Carmen Mendoza ◽  
Nyurky Matheus ◽  
Marta Castro ◽  
Laura Grasa ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Serotonin Transporter ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Molecular Expression

Extracellular Vesicles: A New Nano Tool for the Treatment of Inflammatory Bowel Diseases

2019 ◽  
Vol 15 (6) ◽  
pp. 589-595
Author(s):  
Nitin Tandra ◽  
Peipei Wu ◽  
Xinyuan Hu ◽  
Fei Mao ◽  
Wenrong Xu ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Intestinal Tract ◽  
Intestinal Epithelial Cells ◽  
Therapeutic Strategies ◽  
Intestinal Stem Cells ◽  
Inflammatory Disorder ◽  
Intestinal Epithelial ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The intestinal tract is a complex and important physiological and immunological organ. Intestinal tract homeostasis requires a series of coordinated interactions involving gut microbiota, the crypt intestinal stem cells (ISC) and the surrounding niche, including the intestinal epithelial cells, endothelial cells, dendritic cells, and macrophages. The destruction of intestinal homeostasis leads to autoimmune diseases, such as inflammatory bowel disease (IBD). IBD is a non-specific, and remittent- relapsing inflammatory disorder of the gastrointestinal tract. There is no effective method to keep patients in remission for a long term. It has been reported that extracellular vesicles (EVs) exert immune activation and immunosuppressive effects in the pathogenesis of IBD. In order to explore new therapeutic strategies for IBD, in this review, we summarize the observations on the immune properties and functions of EVs in intestinal mucosal immunity.

Dipeptide transporters in apical and basolateral membranes of the human intestinal cell line Caco-2

1993 ◽  
Vol 265 (2) ◽  
pp. G289-G294 ◽  
Author(s):  
H. Saito ◽  
K. Inui
Keyword(s):  
Cell Line ◽  
Inhibitory Effect ◽  
Intestinal Cell ◽  
Epithelial Cell Line ◽  
Apical Surface ◽  
Intestinal Epithelial ◽  
Basolateral Membranes ◽  
Intestinal Cell Line ◽  
Basolateral Side ◽  
Human Intestinal Cell Line

The localization and transport characteristics of dipeptide transporters of the intestinal epithelial cell line Caco-2 were examined by measuring the intracellular accumulation and transcellular flux of Bestatin, a dipeptide-like anticancer agent. When added to the apical surface of Caco-2 monolayers grown on microporous membrane filters, Bestatin was accumulated in the cells and was transported unidirectionally to the basolateral side. The cellular uptake of Bestatin from the basolateral as well as from the apical surface was inhibited by excess dipeptides. Bestatin accumulation from the apical surface was dependent on the pH of the incubation medium with an optimal pH of 6.0, whereas uptake from the basolateral surface was insensitive to the medium pH. Kinetic parameters for Bestatin uptake also indicated that the basolateral and apical dipeptide transporters could be distinguished from each other. A sulfhydryl reagent, p-chloromercuribenzene sulfonate, inhibited Bestatin accumulation from both surfaces, although the inhibitory effect on the basolateral transport was greater than that on the apical transport. These findings suggest not only that dipeptide transporters exist on both the apical and basolateral membranes of Caco-2 cells but also that the basolateral dipeptide transporter is distinct from the apical H(+)-dipeptide cotransporter.

Search for Compounds Suppressing Intestinal α-Glucosidase Expression in Caco-2 Cells

2019 ◽  
Vol 2 (2) ◽  
pp. 96-101
Author(s):  
Kota Noda ◽  
Eisuke Kato ◽  
Jun Kawabata
Keyword(s):  
Blood Glucose ◽  
Intestinal Tract ◽  
Cell Model ◽  
Epigallocatechin Gallate ◽  
Calluna Vulgaris ◽  
Active Principle ◽  
Intestinal Epithelial ◽  
Mrna Expression Level ◽  
Epicatechin Gallate ◽  
Control Post

Diabetes is a chronic disease characterized by elevated blood glucose level.Reducing carbohydrate absorption from the intestinal tract is an effective strategy to control post-meal blood glucose level. Inhibition of intestinal α-glucosidase, involved in digestion of carbohydrates, is known as an approach to accomplish this. On the other hand, reduction of α-glucosidase amount is expected to work in the similar manner. However, none of the previousstudy pursues this approach. A convenient assay was developed to evaluate α-glucosidase amount employing Caco-2 cells, the intestinal epithelial cell model reported to express α-glucosidase. Sixty plants were screened and two candidate plants, Calluna vulgaris and Perilla frutescens var. crispa were found to reduce α-glucosidase expression. C. vulgaris extract was subjected to activity guided isolation. Proanthocyanidin was identified as the active principle which was analyzed by thiol decomposition to reveal the components as a mixture ofcatechin, epicatechin, epigallocatechin, and A type procyanidin dimer. The proanthocyanidin suppressed about 30% of α-glucosidase amount evaluated through convenient assay, and suppressed bulk of mRNA expression level of sucrase-isomaltase (SI) at 0.125 mg/mL. Several flavan-3-ol monomers were also tested, and epicatechin gallate and epigallocatechin gallate were found to suppress α-glucosidase amount significantly.

scholarly journals Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 160
Author(s):  
Vladana Domazetovic ◽  
Irene Falsetti ◽  
Caterina Viglianisi ◽  
Kristian Vasa ◽  
Cinzia Aurilia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Intestinal Barrier ◽  
Protective Role ◽  
Intercellular Adhesion Molecule ◽  
Intestinal Epithelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Beneficial Effects ◽  
Bowel Diseases

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator.

Tu1198 Intestinal Epithelial Cell Extrusion and Microbial Virulence Are Altered in Pediatric Inflammatory Bowel Diseases

2014 ◽  
Vol 146 (5) ◽  
pp. S-781
Author(s):  
Deenaz Zaidi ◽  
Michael Bording-Jorgenson ◽  
Hien Q. Huynh ◽  
Yuefei Lou ◽  
Julia J. Liu ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Cell Extrusion

Inhibitory effect of carnosine on interleukin-8 production in intestinal epithelial cells through translational regulation

Cytokine ◽  
2008 ◽  
Vol 42 (2) ◽  
pp. 265-276 ◽  
Author(s):  
Dong Ok Son ◽  
Hideo Satsu ◽  
Yoshinobu Kiso ◽  
Mamoru Totsuka ◽  
Makoto Shimizu
Keyword(s):  
Epithelial Cells ◽  
Translational Regulation ◽  
Intestinal Epithelial Cells ◽  
Inhibitory Effect ◽  
Interleukin 8 ◽  
Intestinal Epithelial

Proteomic response of inflammatory stimulated intestinal epithelial cells to in vitro digested plums and cabbages rich in carotenoids and polyphenols

2016 ◽  
Vol 7 (10) ◽  
pp. 4388-4399 ◽  
Author(s):  
Anouk Kaulmann ◽  
Sébastien Planchon ◽  
Jenny Renaut ◽  
Yves-Jacques Schneider ◽  
Lucien Hoffmann ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Epithelial Cells ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Proteomic Response

Proteomic response of intestinal cells as a model of inflammatory bowel diseases to digested plum and cabbage rich in polyphenols and carotenoids.

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