title: Remodeling of Tight Junctions and Enhancement of Barrier Integrity of the CACO-2 Intestinal Epithelial Cell Layer by Micronutrients.
abstract: The micronutrients zinc, quercetin, butyrate, indole and berberine were evaluated for their ability to induce remodeling of epithelial tight junctions (TJs) and enhance barrier integrity in the CACO-2 gastrointestinal epithelial cell culture model. All five of these chemically very diverse micronutrients increased transepithelial electrical resistance (Rt) significantly, but only berberine also improved barrier integrity to the non-electrolyte D-mannitol. Increases of Rt as much as 200% of untreated controls were observed. Each of the five micronutrients also induced unique, signature-like changes in TJ protein composition, suggesting multiple pathways (and TJ arrangements) by which TJ barrier function can be enhanced. Decreases in abundance by as much as 90% were observed for claudin-2, and increases of over 300% could be seen for claudins -5 and -7. The exact effects of the micronutrients on barrier integrity and TJ protein composition were found to be highly dependent on the degree of differentiation of the cell layer at the time it was exposed to the micronutrient. The substratum to which the epithelial layer adheres was also found to regulate the response of the cell layer to the micronutrient. The implications of these findings for therapeutically decreasing morbidity in Inflammatory Bowel Disease are discussed.
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA, 19096, United States of America.
authors.forename: Mary Carmen
authors.initials: MC
authors.lastname: Valenzano
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA, 19096, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: DiGuilio
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA, 19096, United States of America.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mercado
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, 19104, United States of America.
authors.forename: Mimi
authors.initials: M
authors.lastname: Teter
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, 19104, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: To
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, 19104, United States of America.
authors.forename: Brendan
authors.initials: B
authors.lastname: Ferraro
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA, 19096, United States of America.
authors.forename: Brittany
authors.initials: B
authors.lastname: Mixson
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, 19104, United States of America.
authors.forename: Isabel
authors.initials: I
authors.lastname: Manley
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, 19104, United States of America.
authors.forename: Valerissa
authors.initials: V
authors.lastname: Baker
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, 19477, United States of America.
authors.forename: Beverley A
authors.initials: BA
authors.lastname: Moore
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, 19477, United States of America.
authors.forename: Joshua
authors.initials: J
authors.lastname: Wertheimer
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA, 19096, United States of America; Division of Gastroenterology, Lankenau Medical Center, Wynnewood, PA, 19096, United States of America.
authors.forename: James M
authors.initials: JM
authors.lastname: Mullin
mesh_terms: D002087:Butyrates / Q000378:metabolism; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D057167:Claudins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D018977:Micronutrients / Q000378:metabolism*; D011794:Quercetin / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
chemical_list: D002087:Butyrates; D057167:Claudins; D018977:Micronutrients; D011794:Quercetin; D015032:Zinc