title: Modulation of tight junction barrier function by outer membrane proteins of enteropathogenic Escherichia coli: role of F-actin and junctional adhesion molecule-1.
abstract: Enteropathogenic Escherichia coli (EPEC) is a major cause of infantile diarrhea. In this work we investigated the effect of outer membrane proteins (OMP) of EPEC on barrier integrity and the role of actin, junctional adhesion molecule (JAM) and signaling pathways contributing to these changes. Barrier function was assessed by transepithelial electrical resistance (TER). OMP of wild type EPEC, eaeA and maltoporin mutants decreased TER levels of Caco-2 cells. The OMP of espB mutant was deficient in decreasing TER of Caco-2 cells. The proteinase K-digested wild type OMP and EAF mutant OMP did not cause any change in barrier function. Our previous studies have demonstrated that EPEC OMP induced changes in cadherin junctions of Caco-2 cells. Immunofluorescence revealed disruption in actin cytoskeleton by EPEC OMP. However, no change in expression of junctional adhesion molecule-1 was observed. NF-kappaB inhibitor slightly blocked the decrease in TER and protected against actin disruption while ERK1/2 inhibitor had no effect in blocking these changes. In conclusion, our data suggest that the OMP of EPEC alter intestinal barrier function by disrupting actin cytoskeleton and signaling pathways like NF-kappaB may have a role in regulating barrier changes.
authors: Centre for Biotechnology, Anna University, Chennai 600 025, Tamil Nadu, India.
authors: Manjula
authors: M
authors: Puthenedam
authors: Peter H
authors: PH
authors: Williams
authors: B S
authors: BS
authors: Lakshmi
authors: Arun
authors: A
authors: Balakrishnan
mesh_terms: D000199:Actins / Q000502:physiology*; D018829:Adhesins, Bacterial / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D018938:Caco-2 Cells; D015815:Cell Adhesion Molecules / Q000502:physiology*; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000503:physiopathology; D029968:Escherichia coli Proteins / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D062726:Junctional Adhesion Molecules; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000494:pharmacology; D018272:Porins; D011991:Receptors, Virus / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology*
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000199:Actins; D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D015815:Cell Adhesion Molecules; D029968:Escherichia coli Proteins; D005419:Flavonoids; D062726:Junctional Adhesion Molecules; D016328:NF-kappa B; D009570:Nitriles; D018272:Porins; D011991:Receptors, Virus; D013450:Sulfones; C016532:maltoporins; C073819:eaeA protein, E coli; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one