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Title of article :
Effect of a matrix metalloproteinase sequestering biomaterial on Caco-2 epithelial cell barrier integrity in vitro
Author/Authors :
Ailenberg، نويسنده , , Menachem and Sefton، نويسنده , , Michael V.، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2009
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Abstract :
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®-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.
Keywords :
matrix metalloproteinases , Epithelial barrier , MI Theramer™ biomaterial beads , actin cytoskeleton
Journal title :
Acta Biomaterialia
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