title: Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism.
abstract: 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.
authors.affiliation: Dept. of Physiology, Univ. of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: A
authors.initials: A
authors.lastname: Seth
authors.forename: Fang
authors.initials: F
authors.lastname: Yan
authors.forename: D Brent
authors.initials: DB
authors.lastname: Polk
authors.forename: R K
authors.initials: RK
authors.lastname: Rao
mesh_terms: D001426:Bacterial Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D002070:Butadienes / Q000494:pharmacology; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007211:Indoles / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007444:Inulin / Q000378:metabolism; D052201:Lacticaseibacillus rhamnosus / Q000737:chemistry*; D008565:Membrane Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D062793:Occludin; D010539:Permeability; D010750:Phosphoproteins / Q000378:metabolism; D019936:Probiotics / Q000302:isolation & purification / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D064546:Protein Kinase C beta; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D011758:Pyrroles / Q000494:pharmacology; D019108:Tight Junctions / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013997:Time Factors; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002070:Butadienes; C495270:CTNNB1 protein, human; D015820:Cadherins; D007211:Indoles; D008565:Membrane Proteins; D009570:Nitriles; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C569042:TJP1 protein, human; C113580:U 0126; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; C085989:Ro 32-0432; D007444:Inulin; D006861:Hydrogen Peroxide; C497255:PRKCE protein, human; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051744:Protein Kinase C-epsilon; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases