title: The role of caspase-3 in lipopolysaccharide-mediated disruption of intestinal epithelial tight junctions.
abstract: The mechanisms responsible for microbially induced epithelial apoptosis and increased intestinal permeability remain unclear. This study assessed whether purified bacterial lipopolysaccharide (LPS) increases epithelial apoptosis and permeability and whether these changes are dependent on caspase-3 activation. In nontumorigenic epithelial monolayers, Escherichia coli O26:B6 LPS increased apoptosis, as shown by nuclear breakdown, caspase-3 activation, and PARP cleavage, and induced disruption of tight junctional ZO-1. Apical, but not basolateral, exposure to LPS increased epithelial permeability. Addition of a caspase-3 inhibitor abolished the effects of LPS. The findings describe a novel mechanism whereby apical LPS may disrupt epithelial tight junctional ZO-1 and barrier function in a caspase-3-dependent fashion.
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Chin
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Flynn
authors.forename: Jason P
authors.initials: JP
authors.lastname: Fedwick
authors.forename: Andre G
authors.initials: AG
authors.lastname: Buret
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000633:toxicity; D020895:Enterocytes / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D009707:Nucleosomes / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects* / Q000201:enzymology*
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D009707:Nucleosomes; C044101:endotoxin, Escherichia coli; D053148:Caspase 3