Chenodeoxycholic Acid Releases Proinflammatory Cytokines from Small Intestinal Epithelial Cells Through the Farnesoid X Receptor

Horikawa, Tomoki; Oshima, Tadayuki; Li, Min; Kitayama, Yoshitaka; Eda, Hirotsugu; Nakamura, Kumiko; Tamura, Akio; Ogawa, Tomohiro; Yamasaki, Takahisa; Okugawa, Takuya; Kondo, Takashi; Kono, Tomoaki; Tozawa, Katsuyuki; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

doi:10.1159/000496687

Cited by 25 publications

(22 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other bile acid receptors, including FXR, have been reported to have a role in regulating inflammation and barrier function, preventing bacterial translocation out of the intestinal tract and perhaps contributing to the pathogenesis of IBS 8,39 . One such receptor, TGR5, has been shown to inhibit proinflammatory cytokine production 40 .…”

Section: Discussionmentioning

confidence: 99%

“…Bile acids and receptors are thought to be associated with the pathogenesis of IBS. 7,8 In addition to their role in lipid metabolism, bile acids have roles in intestinal motility and inflammation. 9 The levels of primary bile acids in the feces of patients with diarrhea-predominant IBS (IBS-D) correlated with stool consistency and bowel movement frequency when compared with those in healthy subjects.…”

Section: Introductionmentioning

confidence: 99%

“…Bile acids and receptors are thought to be associated with the pathogenesis of IBS 7,8 . In addition to their role in lipid metabolism, bile acids have roles in intestinal motility and inflammation 9 .…”

Section: Introductionmentioning

confidence: 99%

“…Bile acid receptors, including vitamin D receptor (VDR), farnesoid X receptor (FXR), and takeda‐G‐protein‐receptor‐5 (TGR5), are expressed on intestinal epithelial cells and are involved in the functions of bile acids 12 . We previously evaluated the expression levels of bile acid receptors and tight junction related proteins and found that FXR and claudin‐2 (CLDN2) messenger RNA (mRNA) levels were higher in the terminal ileum of patients with IBS than in those of control subjects 8,13 . VDR might have anti‐inflammatory effects and have the relation to somatostatin or tight junction proteins.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Vitamin D receptor is overexpressed in the duodenum of patients with irritable bowel syndrome

Miura

Oshima

Ito

et al. 2020

J of Gastro and Hepatol

Self Cite

View full text Add to dashboard Cite

Background and Aim: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, and bile acids are thought to be associated with the pathogenesis of IBS. Bile acid receptors are expressed on intestinal epithelial cells. However, no study has assessed bile acid receptor proteins in IBS. Therefore, we examined the intestinal mucosal expression of bile acid receptors in patients with IBS. Methods: Intestinal biopsies were performed in patients with IBS and controls. Mast cells, vitamin D receptor (VDR), and somatostatin were stained with specific antibodies. Levels of VDR, farnesoid X receptor (FXR), takeda-G-protein-receptor-5 (TGR5), claudins, and transient-receptor-potential-cation-channel-subfamily-V-member 6 (TRPV6) were assessed by western blotting. Results: 3Mast cell counts in the second part of the duodenum were significantly higher in patients with IBS than in controls. VDR protein levels were significantly elevated in the duodenum and terminal ileum of patients with IBS compared with controls, although this difference was not seen in the cecum or rectum. FXR and TGR5 protein levels did not differ in any part of the intestine. VDR-positive cryptal epithelia in IBS were distributed not only at basal crypt but also along the upper part of the basal crypt epithelial cells. In contrast, the pattern of gut somatostatin-positive cells, claudins, and TRPV6 levels did not differ. Conclusions: The number of mast cells in the duodenum was significantly increased, and the protein expression levels of VDR, but not those of FXR or TGR5, were elevated in the duodenal epithelial crypt in patients with IBS.Recently, the expressions of VDR were reported to be upregulated in the duodenum of patients with functional dyspepsia. 14 However, no study has assessed the levels of bile acid receptor proteins, including VDR, and possible interactions related to bile acid receptors in patients with IBS. We therefore examined the intestinal mucosal expression of bile acid receptors and performed surveillance of reported and related markers in patients with IBS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Vitamin D receptor is overexpressed in the duodenum of patients with irritable bowel syndrome

Miura

Oshima

Ito

et al. 2020

J of Gastro and Hepatol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Medium from the basolateral chamber was collected, and the absorbance of FITCdextran was determined at an excitation wavelength of 485 nm and an emission wavelength of 530 nm using a microplate fluorometer (Infinite M200, Tecan, Austria). The data were expressed as previously described [24].…”

Section: Epithelial Permeability Assaymentioning

confidence: 99%

Glutamine Blocks Interleukin-13-Induced Intestinal Epithelial Barrier Dysfunction

Oshima

Ito

et al. 2019

Digestion

Self Cite

View full text Add to dashboard Cite

Introduction: Impaired intestinal epithelial barrier function is a hallmark of a variety of pathological conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). IBD patients with IBS-like symptoms show higher interleukin-13 (IL-13) serum levels and poor psychological well-being. Supplementary glutamine reduced the daily bowel movement frequency, improved the stool form, and normalized intestinal hyperpermeability. This study was aimed at assessing the effects of IL-13 and supplementary glutamine on human intestinal epithelial function in vitro. Methods: Caco-2 cells were grown on Transwell^TM inserts. IL-13 was added to the basolateral compartment, and transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability measured. Effects of glutamine or the phosphatidylinositol-3-kinase inhibitor LY294002 were assessed. Involvement of tight junction proteins was assessed using Western blotting and immunofluorescence staining. Results: IL-13 significantly decreased TEER and increased FITC labeled-dextran epithelial permeability. IL-13 stimulation decreased the claudin-1 expression and increased the claudin-2 expression. Glutamine alleviated IL-13-induced decrease of TEER and increase of FITC labeled-dextran permeability. Further, the phosphatidylinositol-3-kinase inhibitor showed this alleviating effect while the signal transducer and activator of transcription 6 inhibitor did not. Conclusions: IL-13 induced barrier integrity impairment by decreasing claudin-1 and increasing claudin-2. Glutamine alleviated IL-13-induced barrier dysfunction by increasing claudin-1 expression, via disruption of the phosphatidylinositol-3-kinase/Akt signaling pathway.

show abstract

Bile Acid Derivatives Effectively Prevented High‐Fat Diet‐Induced Colonic Barrier Dysfunction

Shan

Huang

et al. 2023

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope: Bile acids (BAs) have recently emerged as important regulators of many physiological and pathological processes. However, the change of colonic BAs induced by high-fat diet (HFD) and their effects on colonic barrier function remain to be further elucidated. Methods and results: C57BL/6 mice are divided into two groups and feed 12 weeks with diets differing for fat content. Higher levels of serum diamine oxidase (DAO) activity, endotoxin (ET), and d-lactate (d-LA) are observed in HFD-fed mice, indicating an increase in intestinal permeability. Real-time quantitative PCR and western blot analyses demonstrate that HFD downregulates tight junction proteins (TJs, including zonula-occludens 1 [ZO-1], Occludin, and Claudin1) and Muc2 expression in the colon. The colonic BA profiles are analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). HFD induces an increase in primary BAs but a decrease in secondary BAs. In human colonic cell line Caco-2, secondary BAs (deoxycholic acid [DCA], lithocholic acid [LCA], their 3-oxo-and iso-derivates) upregulate the expression of TJs and counteract DSS-induced increase in intestinal permeability at physiological concentrations. IsoDCA and isoLCA are the most effective ones. Moreover, supplementation of isoDCA or isoLCA also effectively prevents HFD-induced colonic barrier dysfunction in mice. Conclusion: These results demonstrate that secondary BAs (especially isomerized derivatives) may be important protectors for the colonic barrier function.

show abstract

Chenodeoxycholic Acid Releases Proinflammatory Cytokines from Small Intestinal Epithelial Cells Through the Farnesoid X Receptor

Cited by 25 publications

References 0 publications

Vitamin D receptor is overexpressed in the duodenum of patients with irritable bowel syndrome

Vitamin D receptor is overexpressed in the duodenum of patients with irritable bowel syndrome

Glutamine Blocks Interleukin-13-Induced Intestinal Epithelial Barrier Dysfunction

Bile Acid Derivatives Effectively Prevented High‐Fat Diet‐Induced Colonic Barrier Dysfunction

Contact Info

Product

Resources

About