TY - JOUR T1 - A Molecular Mechanism for the Anti-Inflammatory Effect of Taurine-Conjugated 5-Aminosalicylic Acid in Inflamed Colon JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1405 LP - 1412 DO - 10.1124/mol.105.020578 VL - 69 IS - 4 AU - Heejung Kim AU - Hyunchu Jeon AU - Hyesik Kong AU - Youngwook Yang AU - Boim Choi AU - Young Mi Kim AU - Len Neckers AU - Yunjin Jung Y1 - 2006/04/01 UR - http://molpharm.aspetjournals.org/content/69/4/1405.abstract N2 - In previous reports, a novel colon-specific prodrug, 5-aminosalicyltaurine (5-ASA-Tau) administered orally, is successfully delivered to and liberates 5-aminosalicylic acid (5-ASA) and taurine in the inflamed large intestine of rats. Furthermore, the prodrug ameliorates the 2,4,6-trinitrobenzene-sulfonic acid-induced colitis, and taurine acts not only as a carrier but also as an active therapeutic agent. In this study, we investigated the anti-inflammatory properties of the prodrug at a molecular level. After rectal administration of taurine, formation of taurine chloramine (TauCl) in the inflamed colonic tissue was examined using high-performance liquid chromatography. In human colon epithelial cell lines, nuclear factor-κB (NF-κB) activity was accessed using an NF-κB-dependent luciferase reporter gene. Protein levels were monitored by Western blotting. DNA binding activity of the NF-κB subunit p65 was determined using a DNA binding assay kit. A millimolar level of TauCl was formed in the inflamed tissue. TauCl inhibited tumor necrosis factor (TNF)-dependent NF-κB activation by modifying thiol(s) on p65 and blocking DNA binding. In addition, 5-ASA inhibited phosphorylation of p65 at serine 536, which is critical for transcriptional activity of NF-κB. Furthermore, combined TauCl/5-ASA treatment additively inhibited TNF-dependent NF-κB activation. Together, our data suggest that the colon-specific carrier taurine contributes to the clinical effect of the prodrug by potentiating the inhibitory effect of the active ingredient 5-ASA on a major proinflammatory signal, TNF-dependent NF-κB activation in the inflamed large intestine. ER -