Mesalazine inhibits activation of transcription factor NF-κB in inflamed mucosa of patients with ulcerative colitis
OBJECTIVES: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-κB plays an important role in inflammatory bowel diseases, we investigated the effects of mesalazine therapy on NF-κB activation in patients with ulcerative colitis.METHODS: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-κB activation using an antibody specific for active NF-κB.RESULTS:In biopsies of active ulcerative colitis but not in noninflamed mucosa, activation of NF-κB was detected predominantly in macrophages. Mesalazine therapy resulted in a strong abrogation of NF-κB activation in situ.CONCLUSIONS:Our results suggest that the therapeutic properties of mesalazine rely at least in part on the inhibition of NF-κB activation, resulting in the suppression of proinflammatory gene expression in the inflamed mucosa.