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-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. 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-kappaB activation using an antibody specific for active NF-kappaB. RESULTS: 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. CONCLUSIONS: 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.
RCT Entities:
OBJECTIVES: The salicylatemesalazine 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. 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-kappaB activation using an antibody specific for active NF-kappaB. RESULTS: 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. CONCLUSIONS: 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.
Authors: Douglas C McVey; Rodger A Liddle; Jennifer Riggs-Sauthier; Nnochiri Ekwuribe; Steven R Vigna Journal: Dig Dis Sci Date: 2005-03 Impact factor: 3.199
Authors: Tamara Aleksic; Bernd Baumann; Martin Wagner; Guido Adler; Thomas Wirth; Christoph K Weber Journal: Gut Date: 2006-07-26 Impact factor: 23.059
Authors: Kenneth H Mellits; Ian F Connerton; Michael F Loughlin; Peter Clarke; Julie Smith; Eleanor Dillon; Phillippa L Connerton; Francis Mulholland; Christopher J Hawkey Journal: BMC Microbiol Date: 2009-02-04 Impact factor: 3.605