33 research outputs found
Omeprazole induces gastric transmucosal permeability to the peptide bradykinin
AIM: To investigate omeprazole-induced transepithelial gastric leak and its effects on the permeability of the peptides bradykinin and oxytocin
M1889 Omeprazole-Induced Transepithelial Leak in Gastric Mucosa: Implications for Small Molecule Drugs and Peptides
Calcitriol modifies tight junctions, improves barrier function, and reduces TNFâαâinduced barrier leak in the human lungâderived epithelial cell culture model, 16HBE 14oâ
Abstract Using the 16HBE 14oâ human airway epithelial cell culture model, calcitriol (Vitamin D) was shown to improve barrier function by two independent metrics â increased transepithelial electrical resistance (TER) and reduced transepithelial diffusion of 14CâDâmannitol (Jm). Both effects were concentration dependent and active out to 168âh postâtreatment. Barrier improvement associated with changes in the abundance of specific tight junctional (TJ) proteins in detergentâsoluble fractions, most notably decreased claudinâ2. TNFâαâinduced compromise of barrier function could be attenuated by calcitriol with a concentration dependence similar to that observed for improvement of control barrier function. TNFâαâinduced increases in claudinâ2 were partially reversed by calcitriol. The ERK 1,2 inhibitor, U0126, itself improved 16HBE barrier function indicating MAPK pathway regulation of 16HBE barrier function. Calcitriol's action was additive to the effect of U0126 in reducing TNFâ α âinduced barrier compromise, suggesting that calcitriol may be acting through a nonâERK pathway in its blunting of TNFâ α â induced barrier compromise. This was supported by calcitriol being without effect on pERK levels elevated by the action of TNFâα. Lack of effect of TNFâ α on the death marker, caspaseâ3, and the inability of calcitriol to decrease the elevated LC3B II level caused by TNFâα, suggest that calcitriol's barrier improvement does not involve a cell death pathway. Calcitriol's improvement of control barrier function was not additive to barrier improvement induced by retinoic acid (Vitamin A). Calcitriol improvement and protection of airway barrier function could in part explain Vitamin D's reported clinical efficacy in COVIDâ19 and other airway diseases
Improvement of Human-Oral-Epithelial-Barrier Function and of Tight Junctions by Micronutrients
Ras Mutation Impairs Epithelial Barrier Function to a Wide Range of Nonelectrolytes
Although ras mutations have been shown to affect epithelial architecture and polarity, their role in altering tight junctions remains unclear. Transfection of a valine-12 mutated ras construct into LLC-PK(1) renal epithelia produces leakiness of tight junctions to certain types of solutes. Transepithelial permeability of d-mannitol increases sixfold but transepithelial electrical resistance increases >40%. This indicates decreased paracellular permeability to NaCl but increased permeability to nonelectrolytes. Permeability increases to d-mannitol (M(r) 182), polyethylene glycol (M(r) 4000), and 10,000-M(r) methylated dextran but not to 2,000,000-M(r) methylated dextran. This implies a âceilingâ on the size of solutes that can cross a ras-mutated epithelial barrier and therefore that the increased permeability is not due to loss of cells or junctions. Although the abundance of claudin-2 declined to undetectable levels in the ras-overexpressing cells compared with vector controls, levels of occludin and claudins 1, 4, and 7 increased. The abundance of claudins-3 and -5 remained unchanged. An increase in extracellular signal-regulated kinase-2 phosphorylation suggests that the downstream effects on the tight junction may be due to changes in the mitogen-activated protein kinase signaling pathway. These selective changes in permeability may influence tumorigenesis by the types of solutes now able to cross the epithelial barrier
Transepithelial leak in Barrett's esophagus patients: The role of proton pump inhibitors
AIM: To determine if the observed paracellular sucrose leak in Barrettâs esophagus patients is due to their proton pump inhibitor (PPI) use
Enhancement of tight junctional barrier function by micronutrients: compound-specific effects on permeability and claudin composition.
Amid an increasing number of reports in the literature concerning epithelial barrier enhancement by various nutrient compounds, there has never been a study performing side-by-side comparisons of these agents in a single epithelial model. We compare five nutrient compounds (previously reported in various epithelial models to enhance barrier function) regarding their ability to increase transepithelial electrical resistance (R(t)) and decrease transepithelial mannitol permeability (J(m)) across LLC-PKâ renal epithelial cell layers. The effects of these nutrients on the abundance of various tight junctional proteins are also compared. In the overall group of nutrients tested--zinc, indole, quercetin, butyrate and nicotine--only nicotine failed to improve barrier function by either parameter. Nicotine also was without effect on tight junctional proteins. Quercetin simultaneously increased R(t) and decreased J(m). Zinc, butyrate and indole only exhibited statistically significant enhancement of R(t). Each of these four effective nutrient compounds had unique patterns of effects on the panel of tight junctional proteins studied. No two compounds produced the same pattern of effects. This unique pattern of effects on tight junctional complex composition by each compound establishes the chance for additive or even synergistic improvement of barrier function by combinations of compounds. A synergistic effect of the combination of quercetin and zinc on R(t) is shown
Su1880 Effects on CaCO-2 Gastrointestinal Epithelial Barrier Properties of the Nutraceuticals Zinc, Berberine, Butyrate, Indole and Quercetin
Remodeling of Tight Junctions and Enhancement of Barrier Integrity of the CACO-2 Intestinal Epithelial Cell Layer by Micronutrients.
The micronutrients zinc, quercetin, butyrate, indole and berberine were evaluated for their ability to induce remodeling of epithelial tight junctions (TJs) and enhance barrier integrity in the CACO-2 gastrointestinal epithelial cell culture model. All five of these chemically very diverse micronutrients increased transepithelial electrical resistance (Rt) significantly, but only berberine also improved barrier integrity to the non-electrolyte D-mannitol. Increases of Rt as much as 200% of untreated controls were observed. Each of the five micronutrients also induced unique, signature-like changes in TJ protein composition, suggesting multiple pathways (and TJ arrangements) by which TJ barrier function can be enhanced. Decreases in abundance by as much as 90% were observed for claudin-2, and increases of over 300% could be seen for claudins -5 and -7. The exact effects of the micronutrients on barrier integrity and TJ protein composition were found to be highly dependent on the degree of differentiation of the cell layer at the time it was exposed to the micronutrient. The substratum to which the epithelial layer adheres was also found to regulate the response of the cell layer to the micronutrient. The implications of these findings for therapeutically decreasing morbidity in Inflammatory Bowel Disease are discussed