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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
| Volume | 273 |
| Issue number | 1 36-1 |
| State | Published - Jul 1997 |
| Externally published | Yes |
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Keywords
- Bile acids
- Colon cancer
- Inflammation
- Nitric oxide synthase
ASJC Scopus subject areas
- Gastroenterology
- Physiology
- Physiology (medical)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Ursodeoxycholate inhibits induction of NOS in human intestinal epithelial cells and in vivo
AU - Invernizzi, Pietro
AU - Salzman, Andrew L.
AU - Szabo, Csaba
AU - Ueta, Ikuya
AU - O'Connor, Michael
AU - Setchell, Kenneth D R
PY - 1997/7
Y1 - 1997/7
N2 - 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.
AB - 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.
KW - Bile acids
KW - Colon cancer
KW - Inflammation
KW - Nitric oxide synthase
UR - http://www.scopus.com/inward/record.url?scp=0030759343&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030759343&partnerID=8YFLogxK
M3 - Article
VL - 273
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
SN - 0193-1849
IS - 1 36-1
ER -