@article {Kim1405, author = {Heejung Kim and Hyunchu Jeon and Hyesik Kong and Youngwook Yang and Boim Choi and Young Mi Kim and Len Neckers and Yunjin Jung}, title = {A Molecular Mechanism for the Anti-Inflammatory Effect of Taurine-Conjugated 5-Aminosalicylic Acid in Inflamed Colon}, volume = {69}, number = {4}, pages = {1405--1412}, year = {2006}, doi = {10.1124/mol.105.020578}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/69/4/1405}, eprint = {https://molpharm.aspetjournals.org/content/69/4/1405.full.pdf}, journal = {Molecular Pharmacology} }