Effect of a matrix metalloproteinase sequestering biomaterial on Caco-2 epithelial cell barrier integrity in vitro.
A novel matrix metalloproteinase sequestering biomaterial (MI Theramer beads) restored the epithelial barrier in a double chamber in vitro test system after disruption by Cytochalasin D and the secretion of the metalloproteinase MMP-2. MI beads are chemically modified (hydroxamated) poly(methacrylic acid-co-methyl methacrylate). We are exploring the utility of this material in inflammatory bowel disease (IBD), in which one manifestation is a compromised intestinal epithelial barrier. In a first step towards this goal we incubated MI beads (or polymethyl methacrylate control beads) with Caco-2 epithelial cells and mesenchymal 3T3 fibroblasts on two sides of a Matrigel((R))-coated filter and used Cytochalasin D (Cyto D) to activate MMP-2 (secreted by the 3T3 cells), disrupt actin filaments of Caco-2 cells and render the epithelial barrier leaky, as measured by dextran fluorescein equilibration. Addition of MI beads to Cyto D-treated cells inhibited active MMP-2 and prevented equilibration of dextran fluorescein. This study is the first step in showing a potential benefit to local (as opposed to systemic) inhibition of metalloproteinases in IBD or other intestinal inflammatory diseases.
Ailenberg
Menachem
M
Institute of Biomaterials and Biomedical Engineering, Department of Chemical Engineering and Applied Chemistry, University of Toronto, Ont., Canada.
Sefton
Michael V
MV
D001672:Biocompatible Materials / Q000008:administration & dosage*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000737:chemistry* / Q000494:pharmacology*
D001672:Biocompatible Materials; D053511:Matrix Metalloproteinase 14