TREFOIL PEPTIDE PROTECTION OF INTESTINAL EPITHELIAL BARRIER FUNCTION - COOPERATIVE INTERACTION WITH MUCIN GLYCOPROTEIN

Background and Aims: Goblet cells secrete a combination of trefoil pep tides and mucin glycoproteins to form a continuous gel on the mucosal surface. The functional effects of these products remain uncertain. Me thods: Trefoil peptides and/or mucin glycoproteins were added to Trans well monolayers of the human colonic cancer-derived T84 cell line. Int act monolayers permitted penetration of <4% of the inert marker [H-3]m annitol at 4 hours. Exposure to the toxic lectin phytohemagglutinin (1 mg/mL), oleic acid (8 mmol/L) and taurocholic acid (12 mmol/L), or Cl ostridium difficile toxin A (0.7 mu g/mL) resulted in loss of barrier function with 36%, 62%, and 45% of [H-3]mannitol penetration, respecti vely. Results: Addition of recombinant human intestinal trefoil factor in physiological concentrations (1-5 mu g/mu L) resulted in attenuati on of the damage to monolayer integrity by up to 52%. Protection was e nhanced (up to 95%) by the copresence of human colonic mucin glycoprot eins. Similar effects were observed when rat intestinal trefoil factor or human spasmolysin, another human trefoil peptide, were added alone or in the presence of human mucin glycoproteins. Conversely, mucin gl ycoproteins isolated from the rat colon or stomach facilitated protect ion when added with human spasmolysin or human intestinal trefoil fact or. Conclusions: Trefoil peptides and mucin glycoproteins protect gast rointestinal mucosa from a variety of insults.