Interferon γ treatment increases endocannabinoid and related <i>N</i>‐acylethanolamine levels in T84 human colon carcinoma cells

Alhouayek, Mireille; Rankin, Linda; Gouveia-Figueira, Sandra; Fowler, Christopher J.

doi:10.1111/bph.14135

Cited by 8 publications

(9 citation statements)

References 41 publications

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“…However, some important differences between previously published studies and this contribution should be highlighted. First, the model used in this report is different from those more commonly adopted in studies on perturbed intestinal permeability in vitro, which usually consist of monocultures of Caco-2 [49,50,51] or other cell lines [52,53,54]. Compared with those models, the co-culture system exploited here [34], based on absorbing (Caco-2) and mucus secreting (HT29-MTX) cells, is closer to the in vivo situation, since the epithelial cell monolayer is covered by a mucus layer.…”

Section: Discussionmentioning

confidence: 99%

Catechin and Procyanidin B2 Modulate the Expression of Tight Junction Proteins but Do Not Protect from Inflammation-Induced Changes in Permeability in Human Intestinal Cell Monolayers

et al. 2019

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The possibility of counteracting inflammation-related barrier defects with dietary compounds such as (poly)phenols has raised much interest, but information is still scarce. We have investigated here if (+)-catechin (CAT) and procyanidin B2 (PB2), two main dietary polyphenols, protect the barrier function of intestinal cells undergoing inflammatory stress. The cell model adopted consisted of co-cultured Caco-2 and HT29-MTX cells, while inflammatory conditions were mimicked through the incubation of epithelial cells with the conditioned medium of activated macrophages (MCM). The epithelial barrier function was monitored through trans-epithelial electrical resistance (TEER), and ROS production was assessed with dichlorofluorescein, while the expression of tight-junctional proteins and signal transduction pathways were evaluated with Western blot. The results indicated that MCM produced significant oxidative stress, the activation of NF-κB and MAPK pathways, a decrease in occludin and ZO-1 expression, and an increase in claudin-7 (CL-7) expression, while TEER was markedly lowered. Neither CAT nor PB2 prevented oxidative stress, transduction pathways activation, ZO-1 suppression, or TEER decrease. However, PB2 prevented the decrease in occludin expression and both polyphenols produced a huge increase in CL-7 abundance. It is concluded that, under the conditions adopted, CAT and PB2 do not prevent inflammation-dependent impairment of the epithelial barrier function of intestinal cell monolayers. However, the two compounds modify the expression of tight-junctional proteins and, in particular, markedly increase the expression of CL-7. These insights add to a better understanding of the potential biological activity of these major dietary flavan-3-ols at intestinal level.

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Section: Discussionmentioning

confidence: 99%

Catechin and Procyanidin B2 Modulate the Expression of Tight Junction Proteins but Do Not Protect from Inflammation-Induced Changes in Permeability in Human Intestinal Cell Monolayers

et al. 2019

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“…The total intake of OEA would be ~1.7 nmol in the low and ~1.4 nmol in high WAZ group, respectively, and the total intake of SEA would be ~1.4 nmol in the low and ~1.2 nmol in the high WAZ group, respectively. Since gastrointestinal epithelial cells express both the NAE hydrolytic enzymes NAAH and FAAH, they are well equipped to metabolize NAEs [ 39 , 40 ]. As a consequence, biological effects exerted by NAEs in human milk would presumably have to be mediated directly upon ingestion, rather than following absorption.…”

Section: Discussionmentioning

confidence: 99%

Satiety Factors Oleoylethanolamide, Stearoylethanolamide, and Palmitoylethanolamide in Mother’s Milk Are Strongly Associated with Infant Weight at Four Months of Age—Data from the Odense Child Cohort

et al. 2018

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Regulation of appetite and food intake is partly regulated by N-acylethanolamine lipids oleoylethanolamide (OEA), stearoylethanolamide (SEA), and palmitoylethanolamide (PEA), which induce satiety through endogenous formation in the small intestine upon feeding, but also when orally or systemic administered. OEA, SEA, and PEA are present in human milk, and we hypothesized that the content of OEA, SEA, and PEA in mother’s milk differed for infants being heavy (high weight-for-age Z-score (WAZ)) or light (low WAZ) at time of milk sample collection. Ultra-high performance liquid chromatography-mass spectrometry was used to determine the concentration of OEA, SEA, and PEA in milk samples collected four months postpartum from mothers to high (n = 50) or low (n = 50) WAZ infants. Associations between OEA, SEA, and PEA concentration and infant anthropometry at four months of age as well as growth from birth were investigated using linear and logistic regression analyses, adjusted for birth weight, early infant formula supplementation, and maternal pre-pregnancy body mass index. Mean OEA, SEA, and PEA concentrations were lower in the high compared to the low WAZ group (all p < 0.02), and a higher concentration of SEA was associated with lower anthropometric measures, e.g., triceps skinfold thickness (mm) (β = −2.235, 95% CI = −4.04, −0.43, p = 0.016), and weight gain per day since birth (g) (β = −8.169, 95% CI = −15.26, −1.08, p = 0.024). This raises the possibility, that the content of satiety factors OEA, SEA, and PEA in human milk may affect infant growth.

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“…Previous in vitro studies used concentrations ranging from 10ng/ml to 100ng/ml of IFN-gamma to induce epithelial barrier dysfunction. 34,38,39 The physiological implication of these concentrations is not known since we do not know the exact local concentrations of IFN-gamma in the mucosa. In the present study, we performed a dose-response study (60-500 ng/ml) to determine the concentration of IFN-gamma required to induce epithelial dysunction in the enteroids.…”

Section: Ifn-gamma Disrupts Epithelial Barrier Function In a Concentrmentioning

confidence: 99%

Lactobacillus rhamnosus GG prevents epithelial barrier dysfunction induced by interferon-gamma and fecal supernatants from irritable bowel syndrome patients in human intestinal enteroids and colonoids

et al. 2018

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Disruption of intestinal barrier homeostasis is an important pathogenic factor in conditions such as irritable bowel syndrome (IBS). Lactobacillus rhamnosus GG (LGG) improves IBS symptoms through unclear mechanisms. Previous studies utilizing colorectal adenocarcinoma cell lines showed that LGG metabolites prevented interferon gamma (IFN-gamma) induced barrier damage but the model employed limited these findings. We aimed to interrogate the protective effects of LGG on epithelial barrier function using human intestinal epithelial cultures (enteroids and colonoids) as a more physiologic model. To investigate how LGG affects epithelial barrier function, we measured FITC-Dextran (FD4) flux across the epithelium as well as tight junction zonula occludens 1 (ZO-1) and occludin (OCLN) expression. Colonoids were incubated with fecal supernatants from IBS patients (IBS-FSN) and healthy controls in the presence or absence of LGG to examine changes in gut permeability. Enteroids incubated with IFN-gamma demonstrated a downregulation of OCLN and ZO-1 expression by 67% and 50%, respectively (p<0.05). This was accompanied by increased paracellular permeability as shown by leakage of FD4. Pretreatment of enteroids with LGG prevented these changes and normalized OCLN and ZO-1 to control levels. These actions were independent of its action against apoptosis. However, these protective effects were not seen with LGG cell wall extracts, LGG DNA, or denatured (boiled) LGG. Intriguingly, IBS-FSN injected into colonoids increased paracellular permeability, which was prevented by LGG. LGG, likely due to secreted proteins, protects against epithelial barrier dysfunction. Bacterial-derived factors to modulate gut barrier function may be a treatment option in disorders such as IBS.

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Interferon γ treatment increases endocannabinoid and related N‐acylethanolamine levels in T84 human colon carcinoma cells

Abstract: IFNγ treatment mobilized endocannabinoid and related NAE levels in T84 cells. However, blockade of anandamide or NAE hydrolysis was insufficient to negate the deleterious effects of this cytokine upon the permeability barrier of the cell monolayers.

Cited by 8 publications

References 41 publications

Catechin and Procyanidin B2 Modulate the Expression of Tight Junction Proteins but Do Not Protect from Inflammation-Induced Changes in Permeability in Human Intestinal Cell Monolayers

Catechin and Procyanidin B2 Modulate the Expression of Tight Junction Proteins but Do Not Protect from Inflammation-Induced Changes in Permeability in Human Intestinal Cell Monolayers

Satiety Factors Oleoylethanolamide, Stearoylethanolamide, and Palmitoylethanolamide in Mother’s Milk Are Strongly Associated with Infant Weight at Four Months of Age—Data from the Odense Child Cohort

Lactobacillus rhamnosus GG prevents epithelial barrier dysfunction induced by interferon-gamma and fecal supernatants from irritable bowel syndrome patients in human intestinal enteroids and colonoids

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