Cell specific effects of glucocorticoid treatment on the NF-kappa Bp65/I kappa B alpha system in patients with Crohn's disease

Background/Aims/Patients-Glucocorticoid cold treatment is known to reduce n uclear factor-kappa B (NF-kappa B)p65 binding activity and activation in la mina propria cells of patients with Crohn's disease. However, lamina propri a cells of glucocorticoid treated patients did not show increased expressio n of I kappa B alpha, and the hypothesised upregulation of I kappa B alpha by glucocorticoid treatment has not yet been shown in vivo. To investigate whether cells other than lamina propria localised mononuclear cells contrib ute to increased I kappa B alpha, resection gut specimens from patients mat ched for Crohn's disease activity index (CDAI) with or without glucocortico id treatment were studied, and changes in the NF-kappa B/I kappa B alpha sy stem were determined in the lamina propria as well as in underlying submuco sal and endothelial cells. Methods-Changes in the NF-kappa B/I kappa B alpha system were determined by immunohistochemistry, electrophoretic mobility shift assay, and western bl ot analysis in resected gut specimens from patients matched for CDAI and va n Hees index with or without long term glucocorticoid treatment. Results-Resection gut specimens from patients with Crohn's disease under gl ucocorticoid treatment had significantly lower nuclear NF-kappa Bp65 levels in mononuclear, epithelial, and endothelial cells than samples from CDAI a nd van Hees index matched patients not having glucocorticoid treatment. Nuc lear NF-kappa Bp65 showed a strong positive correlation with both the CDAI (r = 1 for both groups) and the van Hees index (r = 0.605 for untreated and r = 0.866 for glucocorticoid treated specimens). Lower nuclear translocati on of NF-kappa Bp65 in the glucocorticoid treated group was paralleled by h igher I kappa B alpha levels in vascular endothelial cells, but not in infi ltrating mononuclear cells. Conclusion-A comparison of resection gut specimens from untreated and treat ed CDAI matched patients with Crohn's disease showed downregulation of NF-k appa B binding activity and NF-kappa Bp65 expression and cell specific indu ction of endothelial I kappa B kappa expression in the glucocorticoid treat ed group. As the two groups showed similar disease activity (CDAI, van Hees index), the activation of the NF-kappa Bp65/I kappa B alpha system must be only part of the inflammatory cascade leading to the clinical appearance o f Crohn's disease.