An anti-inflammatory mechanism of taurine conjugated 5-aminosalicylic acid against experimental colitis: Taurine chloramine potentiates inhibitory effect of 5-aminosalicylic acid on IL-1β-mediated NFκB activation

Previously, we reported that oral administration of taurine conjugated 5-aminosalicylic acid, a colon-specific prodrug of 5-aminosalicylic acid (5-ASA), is effective in ameliorating experimental colitis and taurine elicits an additive anti-inflammatory effect upon cotreatment with 5-ASA. To explore a molecular mechanism for the anti-inflammatory property of the prodrug, we investigated the effect of the conjugate on IL-1 beta-mediated NF kappa B activation. in human colon carcinoma Caco-2 and HCT116 cells, NF kappa B activity was accessed by a luciferase reporter assay and IL-6 secretion. Protein levels were determined by Western blotting. IL-6 levels were monitored by an Elisa kit. Treatment with either 5-ASA or taurine chloramine (TauCl) inhibited IL-1 beta-mediated NF kappa B dependent luciferase expression and IL-6 secretion. In HCT116 cells, the inhibitory effect by TauCl or 5-ASA was through preventing IL-1 beta-induced I kappa B kinase activation and subsequently interfering with I kappa B alpha degradation and p65 nuclear accumulation. Furthermore, combined TauCl/5-ASA treatment interfered additively with the activation process, leading to additive inhibitory effect on IL-1 beta-mediated NF kappa B activation. Our results suggest that the anti-inflammatory effect of the prodrug on experimental colitis is attributed to the inhibition of the IL-1 beta-mediated NF kappa B activation and the taurine effect is through TauCl potentiating the ability of 5-ASA to inhibit IL-1 beta dependent NF kappa B activation. (C) 2009 Elsevier B.V. All rights reserved.