The induction of colonocyte differentiation in CaCo-2 cells by sodium butyrate causes an increase in glucosylceramide synthesis in order to avoid apoptosis based on ceramide

Yamane, Mototeru; Yamane, Sayoko

doi:10.1016/j.abb.2007.01.008

Cited by 16 publications

(9 citation statements)

References 45 publications

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“…Enterocyte differentiation marker Alpi was increased with exposure to all SCFAs, especially BUT and PROP. This is consistent with previous results that have shown potent anti-proliferative HDAC activity of BUT and PROP [27,28]. SCFAs have also been shown to stimulate mucin production and secretion [29,30].…”

Section: Plos Onesupporting

confidence: 93%

Intestinal enteroids recapitulate the effects of short-chain fatty acids on the intestinal epithelium

et al. 2020

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Enteroids are cultured primary intestinal epithelial cells that recapitulate epithelial lineage development allowing for a more complex and physiologically relevant model for scientific study. The large presence of intestinal stem cells (ISC) in these enteroids allows for the study of metabolite effects on cellular processes and resulting progeny cells. Short-chain fatty acids (SCFA) such as butyrate (BUT) are bacterial metabolites produced in the gastrointestinal tract that are considered to be beneficial to host cells. Therefore, the objective was to study the effects of SCFAs on biomarkers of ISC activity, differentiation, barrier function and epithelial defense in the intestine using mouse and human enteroid models. Enteroids were treated with two concentrations of acetate (ACET), propionate (PROP), or BUT for 24 h. Enteroids treated with BUT or PROP showed a decrease in proliferation via EdU uptake relative to the controls in both mouse and human models. Gene expression of Lgr5 was shown to decrease with BUT and PROP treatments, but increased with ACET. As a result of BUT and PROP treatments, there was an increase in differentiation markers for enterocyte, Paneth, goblet, and enteroendocrine cells. Gene expression of antimicrobial proteins Reg3β, Reg3γ, and Defb1 were stimulated by BUT and PROP, but not by ACET which had a greater effect on expression of tight junction genes Cldn3 and Ocln in 3D enteroids. Similar results were obtained with human enteroids treated with 10 mM SCFAs and grown in either 3D or Trans-well™ model cultures, although tight junctions were influenced by BUT and PROP, but not ACET in monolayer format. Furthermore, BUT and PROP treatments increased transepithelial electrical resistance after 24 h compared to ACET or control. Overall, individual SCFAs are potent stimulators of cellular gene expression, however, PROP and especially BUT show great efficacy for driving cell differentiation and gene expression.

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Section: Plos Onesupporting

confidence: 93%

Intestinal enteroids recapitulate the effects of short-chain fatty acids on the intestinal epithelium

et al. 2020

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“…Together with the much faster effects of SCFA on TER and the different specificity among each SCFA, the findings on the effects of SCFA on colonic barrier functions shown in the present study represent a distinct phenomenon and mechanism from previous observations. The long-term action of butyrate in Caco-2 monolayers shown in the previous reports is associated with the promotive effect of butyrate on cell differentiation (18,19) . On the other hand, Mariadason et al showed that butyrate at 10 mmol/l increased colonic mucosal permeability and decreased TER (31) .…”

Section: Discussionmentioning

confidence: 69%

Physiological concentrations of short-chain fatty acids immediately suppress colonic epithelial permeability

2008

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Colonic fermentation products, SCFA, have various effects on colonic functions. Here, we found that physiological concentrations of SCFA immediately promote epithelial barrier function in the large intestine. Solutions of mixed and individual SCFA were applied to the caecal walls mounted on Ussing-type chambers. Transepithelial electrical resistance (TER) increased rapidly and reached a peak 35 % higher than that in the control specimen within 10 min post application of the SCFA mixture (80 acetate, 40 propionate, 20 butyrate (mmol/l)). The Lucifer yellow permeability, a paracellular transport marker, was dose-dependently reduced by the mixed SCFA, acetate and propionate solutions. Inhibition of monocarboxylate transporter-1 did not influence the increase in TER with acetate; however, lowering the pH (from 7·5 to 5·5) clearly enhanced the effect of acetate. Non-metabolizable, bromo and chloro derivatives of SCFA also increased TER. These results suggest that passive diffusion of SCFA is dominant and the metabolism of SCFA is not required for the promotive effect of SCFA on barrier function. We also observed that individual SCFA dose-dependently increased TER in T84 and Caco-2 cells, which indicates that SCFA directly stimulate epithelial cells. Depletion of membrane cholesterol and inhibitors of phosphatidylinositol-3 kinase and Gq protein attenuated the acetate-mediated promotive effect. Finally, we found that the mucosal application of the SCFA mixture dose-dependently suppressed [ 3 H] mannitol transport from the caecal lumen to the mesenteric blood in the anaesthetized rats. We conclude that physiological concentrations of SCFA immediately enhance barrier function of the colonic epithelium through cholesterol-rich microdomain in the plasma membrane.

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“…To investigate whether B. cereus adheres to the cell surface based on interaction between flagellin and Gb3, we used a combination of two methods to prepare these cells for experiments: pre-treatment of CaCo-2 cells with D, L- erythro -1-phenyl-2-decanoylamino-3-morpholino-1-propanol•HCl PDMP (27 μM, 3 days) [ 35 , 36 ] to block the biosynthesis of Gb3, or pre-treatment with a high concentration of LecA (3 μg/ml) or purified flagellin (3 μg/ml) to preclude B. cereus from binding to Gb3. We then conducted an adhesion assay using colony plate counting and found that pre-treated CaCo-2 cells associated with significantly fewer B. cereus cells than did unmodified CaCo-2 cells ( Figure 4(f )).…”

Section: Resultsmentioning

confidence: 99%

The interaction between flagellin and the glycosphingolipid Gb3 on host cells contributes to Bacillus cereus acute infection

Gao

Huang

et al. 2020

Virulence

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Bacillus cereus is an opportunistic pathogen that can cause emetic or diarrheal foodborne illness. Previous studies have identified multiple pathogenic B. cereus strains and characterized a variety of virulence factors. Here, we demonstrate that the virulence and lethality of B. cereus for mammalian cells and host animals involve the interaction of B. cereus flagellin proteins and the host-cell-surface-localized glycosphingolipid Gb3 (CD77, Galα1-4Galβ1-4Glcβ1-Cer). We initially found that B. cereus infection was less lethal for Gb3-deficiencient A4galt −/- mice than for wild-type mice. Subsequent experiments established that some factor other than secreted toxins must account of the observed differential lethality: Gb3-deficiencient A4galt −/- mice were equally susceptible to secreted-virulence-factor-mediated death as WT mice, and we observed no differences in the bacterial loads of spleens or livers of mice treated with B. cereus strain vs. mice infected with a mutant variant of incapable of producing many secreted toxins. A screen for host-interacting B. cereus cell wall components identified the well-known flagellin protein, and both flagellin knockout strain assays and Gb3 inhibitor studies confirmed that flagellin does interact with Gb3 in a manner that affects B. cereus infection of host cells. Finally, we show that treatment with polyclonal antibody against flagellin can protect mice against B. cereus infection. Thus, beyond demonstrating a previously unappreciated interaction between a bacterial motor protein and a mammalian cell wall glycosphingolipid, our study will provide useful information for the development of therapies to treat infection of B. cereus .

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The induction of colonocyte differentiation in CaCo-2 cells by sodium butyrate causes an increase in glucosylceramide synthesis in order to avoid apoptosis based on ceramide

Cited by 16 publications

References 45 publications

Intestinal enteroids recapitulate the effects of short-chain fatty acids on the intestinal epithelium

Intestinal enteroids recapitulate the effects of short-chain fatty acids on the intestinal epithelium

Physiological concentrations of short-chain fatty acids immediately suppress colonic epithelial permeability

The interaction between flagellin and the glycosphingolipid Gb3 on host cells contributes to Bacillus cereus acute infection

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