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Molecular Pharmacology

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Research ArticleArticle

A Molecular Mechanism for the Anti-Inflammatory Effect of Taurine-Conjugated 5-Aminosalicylic Acid in Inflamed Colon

Heejung Kim, Hyunchu Jeon, Hyesik Kong, Youngwook Yang, Boim Choi, Young Mi Kim, Len Neckers and Yunjin Jung
Molecular Pharmacology April 2006, 69 (4) 1405-1412; DOI: https://doi.org/10.1124/mol.105.020578
Heejung Kim
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Hyunchu Jeon
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Hyesik Kong
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Youngwook Yang
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Boim Choi
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Young Mi Kim
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Len Neckers
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Yunjin Jung
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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.

  • Received November 4, 2005.
  • Accepted January 3, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 69 (4)
Molecular Pharmacology
Vol. 69, Issue 4
1 Apr 2006
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Research ArticleArticle

A Molecular Mechanism for the Anti-Inflammatory Effect of Taurine-Conjugated 5-Aminosalicylic Acid in Inflamed Colon

Heejung Kim, Hyunchu Jeon, Hyesik Kong, Youngwook Yang, Boim Choi, Young Mi Kim, Len Neckers and Yunjin Jung
Molecular Pharmacology April 1, 2006, 69 (4) 1405-1412; DOI: https://doi.org/10.1124/mol.105.020578

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Research ArticleArticle

A Molecular Mechanism for the Anti-Inflammatory Effect of Taurine-Conjugated 5-Aminosalicylic Acid in Inflamed Colon

Heejung Kim, Hyunchu Jeon, Hyesik Kong, Youngwook Yang, Boim Choi, Young Mi Kim, Len Neckers and Yunjin Jung
Molecular Pharmacology April 1, 2006, 69 (4) 1405-1412; DOI: https://doi.org/10.1124/mol.105.020578
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