Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism.

Seth A, Yan F, Polk DB, Rao RK
Am J Physiol Gastrointest Liver Physiol. 2008 294 (4): G1060-9

PMID: 18292183 · PMCID: PMC2653458 · DOI:10.1152/ajpgi.00202.2007

Probiotics promote intestinal epithelial integrity and reduce infection and diarrhea. We evaluated the effect of Lactobacillus rhamnosus GG-produced soluble proteins (p40 and p75) on the hydrogen peroxide-induced disruption of tight junctions and barrier function in Caco-2 cell monolayers. Pretreatment of cell monolayers with p40 or p75 attenuated the hydrogen peroxide-induced decrease in transepithelial resistance and increase in inulin permeability in a time- and dose-dependent manner. p40 and p75 also prevented hydrogen peroxide-induced redistribution of occludin, ZO-1, E-cadherin, and beta-catenin from the intercellular junctions and their dissociation from the detergent-insoluble fractions. Both p40 and p75 induced a rapid increase in the membrane translocation of PKCbetaI and PKCepsilon. The attenuation of hydrogen peroxide-induced inulin permeability and redistribution of tight junction proteins by p40 and p75 was abrogated by Ro-32-0432, a PKC inhibitor. p40 and p75 also rapidly increased the levels of phospho-ERK1/2 in the detergent-insoluble fractions. U0126 (a MAP kinase inhibitor) attenuated the p40- and p75-mediated reduction of hydrogen peroxide-induced tight junction disruption and inulin permeability. These studies demonstrate that probiotic-secretory proteins protect the intestinal epithelial tight junctions and the barrier function from hydrogen peroxide-induced insult by a PKC- and MAP kinase-dependent mechanism.

MeSH Terms (32)

Bacterial Proteins beta Catenin Butadienes Caco-2 Cells Cadherins Dose-Response Relationship, Drug Electric Impedance HT29 Cells Humans Hydrogen Peroxide Indoles Intestinal Mucosa Inulin Lactobacillus rhamnosus Membrane Proteins Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Nitriles Occludin Permeability Phosphoproteins Probiotics Protein Kinase C Protein Kinase C-epsilon Protein Kinase C beta Protein Kinase Inhibitors Protein Transport Pyrroles Tight Junctions Time Factors Zonula Occludens-1 Protein

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