title: LPS Induces Hyper-Permeability of Intestinal Epithelial Cells.
abstract: Necrotizing Enterocolitis (NEC) is a severe inflammatory disorder leading to high morbidity and mortality rates. A growing body of evidence demonstrate the key role of the Toll like receptor 4 (TLR4) in NEC. This membranal receptor recognizes lipopolysaccharides (LPS) from the bacterial wall and triggers an inflammatory response. The aim of the present study was to elucidate the effect of LPS on paracellular permeability known to be severely affected in NEC. IEC-18 cells were treated with LPS and the effects on morphology, paracellular permeability and their associated gene and protein expressions were measured. Our results show that LPS down regulated the expression of occludin and ZO-1 mRNAs while up regulating Cdkn1a. In addition LPS caused a significant increase in paracellular permeability and epithelial barrier damage. Finally ZO-1 protein was found to be spatially disarrayed in the intercellular junctions in response to LPS. We conclude that LPS adversely affected the functionality of the intestinal epithelial barrier suggesting a new mechanism by which bacterial infection may contribute to the development of NEC. J. Cell. Physiol. 232: 381-390, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: The Hebrew University of Jerusalem, School of Nutritional Sciences, Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, Rehovot, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Bein
authors.affiliation: The Hebrew University of Jerusalem, The Racah Institute of Physics, Jerusalem, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zilbershtein
authors.affiliation: The Hebrew University of Jerusalem, The Racah Institute of Physics, Jerusalem, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Golosovsky
authors.affiliation: The Hebrew University of Jerusalem, The Racah Institute of Physics, Jerusalem, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Davidov
authors.affiliation: The Hebrew University of Jerusalem, School of Nutritional Sciences, Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, Rehovot, Israel. betty.schwartz@mail.huji.ac.il.
authors.forename: Betty
authors.initials: B
authors.lastname: Schwartz
mesh_terms: D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007422:Intestines / Q000166:cytology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020349:Surface Plasmon Resonance; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D062826:Zonula Occludens-1 Protein