Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis.

Abstract

The salicylate mesalazine is commonly used for the treatment of inflammatory bowel diseases, yet its precise mechanism of action is unknown. Because transcription factor NF-kappaB plays an important role in inflammatory bowel diseases, we investigated the effects of mesalazine therapy on NF-kappaB activation in patients with ulcerative colitis. A total of 20 patients with moderately active ulcerative colitis received mesalazine for 8 wk. Biopsies were taken before and after drug administration and analyzed for NF-kappaB activation using an antibody specific for active NF-kappaB. In biopsies of active ulcerative colitis but not in noninflamed mucosa, activation of NF-kappaB was detected predominantly in macrophages. Mesalazine therapy resulted, in a strong abrogation of NF-kappaB activation in situ. Our results suggest that the therapeutic properties of mesalazine rely at least in part on the inhibition of NF-kappaB activation, resulting in the suppression of proinflammatory gene expression in the inflamed mucosa.