Ursodeoxycholate inhibits induction of NOS in human intestinal epithelial cells and in vivo

Pietro Invernizzi, Andrew L. Salzman, Csaba Szabo, Ikuya Ueta, Michael O'Connor, Kenneth D R Setchell

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Ursodeoxycholate (UDCA) has anti-inflammatory and chemoprotective effects in animal models of inflammatory bowel disease and colon cancer. Because overproduction of nitric oxide (NO) by the inducible isoform of NO synthase (iNOS) is implicated in the pathogenesis of these conditions, we investigated the ability of UDCA to inhibit NO production in transformed human intestinal epithelial (DLD-1) cells. Nitrite/nitrate production was measured by the Griess reaction, enzymatic activity of iNOS was assessed by conversion of L-arginine to L-citrulline, and protein and mRNA were measured by Western and Northern blotting. Dose-dependent inhibition of interleukin- 1β- and interferon-γ-stimulated nitrite/nitrate production was observed when cells were preincubated for 6 h with UDCA (0-800 μM), and a substantial inhibition (81 ± 3.2%) was seen at 500 μM. In cytokine-stimulated cells, UDCA reduced iNOS mRNA, protein, and enzyme activity without exerting cytotoxicity. UDCA had a minimal direct inhibitory effect on iNOS enzyme activity. UDCA pretreatment also reduced the expression of iNOS in the colonic epithelium of rats treated with bacterial lipopolysaccharide. Thus UDCA inhibits the induction of epithelial iNOS in vitro and in vivo, and this effect may contribute to the anti-inflammatory and chemoprotective actions of UDCA.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume273
Issue number1 36-1
StatePublished - Jul 1997
Externally publishedYes

Fingerprint

Protein Isoforms
Nitric Oxide Synthase
Epithelial Cells
Nitrites
Nitrates
Nitric Oxide
Anti-Inflammatory Agents
Citrulline
Messenger RNA
Nitric Oxide Synthase Type II
Enzymes
Interleukin-1
Inflammatory Bowel Diseases
Northern Blotting
Colonic Neoplasms
Interferons
Lipopolysaccharides
Arginine
Proteins
Epithelium

Keywords

  • Bile acids
  • Colon cancer
  • Inflammation
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Invernizzi, P., Salzman, A. L., Szabo, C., Ueta, I., O'Connor, M., & Setchell, K. D. R. (1997). Ursodeoxycholate inhibits induction of NOS in human intestinal epithelial cells and in vivo. American Journal of Physiology - Gastrointestinal and Liver Physiology, 273(1 36-1).

Ursodeoxycholate inhibits induction of NOS in human intestinal epithelial cells and in vivo. / Invernizzi, Pietro; Salzman, Andrew L.; Szabo, Csaba; Ueta, Ikuya; O'Connor, Michael; Setchell, Kenneth D R.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 273, No. 1 36-1, 07.1997.

Research output: Contribution to journalArticle

Invernizzi, P, Salzman, AL, Szabo, C, Ueta, I, O'Connor, M & Setchell, KDR 1997, 'Ursodeoxycholate inhibits induction of NOS in human intestinal epithelial cells and in vivo', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 273, no. 1 36-1.
Invernizzi, Pietro ; Salzman, Andrew L. ; Szabo, Csaba ; Ueta, Ikuya ; O'Connor, Michael ; Setchell, Kenneth D R. / Ursodeoxycholate inhibits induction of NOS in human intestinal epithelial cells and in vivo. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 1997 ; Vol. 273, No. 1 36-1.
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