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

Eur J Pharmacol. 2009 Sep 15;618(1-3):91-7. doi: 10.1016/j.ejphar.2009.07.009. Epub 2009 Jul 17.


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-1beta-mediated NFkappaB activation. In human colon carcinoma Caco-2 and HCT116 cells, NFkappaB 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-1beta-mediated NFkappaB dependent luciferase expression and IL-6 secretion. In HCT116 cells, the inhibitory effect by TauCl or 5-ASA was through preventing IL-1beta-induced IkappaB kinase activation and subsequently interfering with IkappaBalpha degradation and p65 nuclear accumulation. Furthermore, combined TauCl/5-ASA treatment interfered additively with the activation process, leading to additive inhibitory effect on IL-1beta-mediated NFkappaB activation. Our results suggest that the anti-inflammatory effect of the prodrug on experimental colitis is attributed to the inhibition of the IL-1beta-mediated NFkappaB activation and the taurine effect is through TauCl potentiating the ability of 5-ASA to inhibit IL-1beta dependent NFkappaB activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Cell Line, Tumor
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Enzyme Activation / drug effects
  • Humans
  • I-kappa B Kinase / metabolism
  • Interleukin-1beta / metabolism*
  • Mesalamine / chemistry*
  • Mesalamine / pharmacology*
  • Mesalamine / therapeutic use
  • NF-kappa B / metabolism*
  • Prodrugs / metabolism
  • Taurine / analogs & derivatives*
  • Taurine / chemistry
  • Taurine / pharmacology


  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • NF-kappa B
  • Prodrugs
  • Taurine
  • Mesalamine
  • N-chlorotaurine
  • I-kappa B Kinase