Abstract
BackgroundCeliac disease is characterized by enhanced intestinal paracellular permeability due to alterations of function and expression of tight junction (TJ) proteins including ZO-1, Claudin-1 and Occludin. Polyamines are pivotal in the control of intestinal barrier function and are also involved in the regulation of intercellular junction proteins. Different probiotic strains may inhibit gliadin-induced toxic effects and the Lactobacillus rhamnosus GG (L.GG) is effective in the prevention and treatment of gastrointestinal diseases. Aims of the study were to establish in epithelial Caco-2 cells whether i) gliadin affects paracellular permeability and polyamine profile; ii) co-administration of viable L.GG, heat-killed L.GG (L.GG-HK) or its conditioned medium (L.GG-CM) preserves the intestinal epithelial barrier integrity. Additionally, the effects of L.GG on TJ protein expression were tested in presence or absence of polyamines.ResultsAdministration of gliadin (1 mg/ml) to Caco-2 cells for 6 h caused a significant alteration of paracellular permeability as demonstrated by the rapid decrease in transepithelial resistance with a concomitant zonulin release. These events were followed by a significant increase in lactulose paracellular transport and a slight lowering in ZO-1 and Occludin expression without affecting Claudin-1. Besides, the single and total polyamine content increased significantly. The co-administration of viable L.GG (108 CFU/ml), L.GG-HK and L.GG-CM with gliadin significantly restored barrier function as demonstrated by transepithelial resistance, lactulose flux and zonulin release. Viable L.GG and L.GG-HK, but not L.GG-CM, led to a significant reduction in the single and total polyamine levels. Additionally, only the co-administration of viable L.GG with gliadin significantly increased ZO-1, Claudin-1 and Occludin gene expression compared to control cells. When Caco-2 cells treated with viable L.GG and gliadin were deprived in the polyamine content by α-Difluoromethylornithine, the expression of TJ protein mRNAs was not significantly different from that in controls or cells treated with gliadin alone.ConclusionsGliadin modifies the intestinal paracellular permeability and significantly increases the polyamine content in Caco-2 cells. Concomitant administration of L.GG is able to counteract these effects. Interestingly, the presence of cellular polyamines is necessary for this probiotic to exert its capability in restoring paracellular permeability by affecting the expression of different TJ proteins.
Highlights
Celiac disease is characterized by enhanced intestinal paracellular permeability due to alterations of function and expression of tight junction (TJ) proteins including ZO-1, Claudin-1 and Occludin
The presence of cellular polyamines is necessary for this probiotic to exert its capability in restoring paracellular permeability by affecting the expression of different Tight junction (TJ) proteins
Effects of gliadin and L.GG treatments on Caco-2 monolayer barrier function (TER and lactulose flux) transepithelial resistance (TER) measurements were determined after the addition of viable L.GG, L.GG-Heat killed (HK) and L.GG-conditioned medium (CM) to polarized monolayers of Caco-2 cells seeded on Transwell filter inserts
Summary
Celiac disease is characterized by enhanced intestinal paracellular permeability due to alterations of function and expression of tight junction (TJ) proteins including ZO-1, Claudin-1 and Occludin. CD is characterized by enhanced paracellular permeability and an impairment in the integrity of the intestinal barrier [2] that allows the interactions of gluten peptides with antigen-presenting cells in the lamina propria. Gliadin is rich in glutamine and the presence of numerous glutamine acceptor proteins in the extracellular matrix could be responsible for the formation of crosslinks between gliadin and matrix proteins. This gliadin immobilization to extracellular matrix proteins could provide a long-term availability of toxic gliadin fractions in the mucosa [3]. There is still much debate about the possible interactions of gliadin (and/or its peptide derivatives) with intestinal epithelia and the mechanism(s) through which it crosses the epithelial barrier to reach the submucosa [4]
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