Background/Aims: The lectin phytohemagglutinin is a mitogen for intestinal epithelial cells in vivo. The mechanisms of action are unknown and were therefore analyzed in vitro. Methods: Human (Intestine-407) and rat (IEC-6; IEC-18) intestinal epithelial cell lines were stimulated with phytohemagglutinin. Proliferation was assayed by 3H-thymidine incorporation, activation of mitogen-activated protein kinase (MAPK) by Western blotting, and induction of c-fos mRNA expression by semiquantitative polymerase chain reaction. Control experiments were performed with phenyl-N-acetyl-α-D-galactosaminide or the tyrosine kinase inhibitor tyrphostin A25. Results: Phytohemagglutinin (0.1 µg/ml) significantly stimulated proliferation in all three cell lines after 48–72 h. MAPK activation was detected after 15–30 min, and an induction of c-fos mRNA expression after 15– 30 min of stimulation. Mitogenic effects were blocked by preincubation with phenyl-N-acetyl-α-D-galactosaminide or tyrphostin A25. Conclusion: Phytohemagglutinin stimulated proliferation, MAPK activation and induction of c-fos mRNA expression. The lectin may contribute to intestinal mucosal growth and regeneration thereby preventing gut atrophy.

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