Mesalazine inhibits activation of transcription factor NF-kappa B 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 unknow n. Because transcription factor NF-kappaB plays an important role in inflam matory bowel diseases, we investigated the effects of mesalazine therapy on NF-kappaB activation in patients with ulcerative colitis. METHODS: A total of 20 patients with moderately active ulcerative colitis r eceived mesalazine for 8 wk. Biopsies were taken before and after drug admi nistration and analyzed for NF-kappaB activation using an antibody specific for active NF-kappaB. RESULTS: In biopsies of active ulcerative colitis but not in noninflamed mu cosa, activation of NF-kappaB was detected predominantly in macrophages. Me salazine therapy resulted in a strong abrogation of NF-kappaB activation in situ. CONCLUSIONS: Our results suggest that the therapeutic properties of mesalaz ine rely at least in part on the inhibition of NF-kappaB activation, result ing in the suppression of proinflammatory gene expression in the inflamed m ucosa. (C) 2000 by Am. Cell. of Gastroenterology.