Vasoactive intestinal peptide inhibits adhesion molecule expression in activated human colon serosal fibroblasts by preventing NF-kappaB activation.

Background: Stricture formation in Crohn's disease (CD) occurs as a result of persistent intestinal inflammatory activation, which leads to enhanced adhesion molecule expression in serosal fibroblasts (SFs). Vasoactive intestinal peptide (VIP) has anti-inflammatory and immunoregulatory properties. Treatment with VIP prevents experimental CD in animal models at the clinical and pathologic levels. The present study reports the effect of VIP on the expression of intracellular adhesion molecule-1 (ICAM-1) in IL-1beta-stimulated human colon SFs.

Materials And Methods: Primary human colon SFs were incubated with or without IL-1beta (10 ng/mL) in the presence or absence of VIP at various concentrations (0.1 to 100 nM) for designated time. Cell surface and cytosolic ICAM-1 expression were evaluated by flow cytometry and Western blot analysis, respectively. The DNA binding capacity of NF-kappaB was analyzed by electrophoretic mobility shift assay. The phosphorylation of IkappaB-alpha was examined by Western blot analysis.

Results: VIP inhibited IL-1beta-induced expression of ICAM-1 in a dose-dependent manner. The IL-1beta-induced ICAM-1 was also inhibited by a potent inhibitor of NF-kappaB, MG132. VIP also decreased IL-1beta-induced NF-kappaB DNA binding capacity and phosphorylation of IkappaB-alpha.

Conclusion: VIP has an inhibitory effect on IL-1beta-induced ICAM-1 expression in SFs, which may be associated with NF-kappaB activity. This may make VIP potentially a novel therapeutic agent for preventing stricture formation in Crohn's disease.