Format

Send to

Choose Destination
Mol Cell Biochem. 2010 Mar;336(1-2):17-24. doi: 10.1007/s11010-009-0259-2. Epub 2009 Oct 3.

TNF-alpha modulates iNOS expression in an experimental rat model of indomethacin-induced jejunoileitis.

Author information

1
Division of Gastroenterology, Department of Medicine, State University of New York, Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. nandij@upstate.edu

Abstract

Multiple mucosal immune factors, such as TNF-alpha and IL-1beta, are thought to be key mediators involved in inflammatory bowel disease. We evaluated the role of the pro-inflammatory cytokine TNF-alpha on nitric oxide synthase (NOS) expression in indomethacin-induced jejunoileitis in rats. Jejunoileitis was induced in rats with subcutaneous injections of indomethacin (7.5 mg/kg) 24 h apart for two consecutive days, and animals were randomized into four groups. Group 1 received only indomethacin. Group 2 was treated with a daily dose of phosphodiesterase (PDE) inhibitor (theophylline or pentoxifylline) by oral gavage for 2 days before and 4 days after indomethacin. Group 3 received a single dose of anti-TNF-alpha monoclonal antibody (TNF-Ab, IP) 30 min before indomethacin. Group 4 was treated with 1 h hyperbaric oxygenation (HBO(2)) for 5 days after indomethacin. Rats were sacrificed at 12 h or 4 days after final indomethacin injection. PDE inhibitor, TNF-Ab, or HBO(2) treatment significantly decreased indomethacin-induced ulceration, myeloperoxidase activity, and disease activity index. Although indomethacin significantly increased serum TNF-alpha and nitrate/nitrite (NOx) concentrations above control values at 12 h, inducible NOS (iNOS) expression was detected only at day 4. Serum IL-1beta levels did not change at 12 h but increased 4-fold after 4 days. Indomethacin had no effect on constitutive NOS. Treatment with PDE inhibitor, TNF-Ab, or HBO(2) significantly reduced serum/tissue TNF-alpha, IL-1beta, NOx, and iNOS expression. Our data show TNF-alpha plays an early pro-inflammatory role in indomethacin-induced jejunoileitis. Additionally, down-regulation of NOx by PDE inhibitors, TNF-Ab, or HBO(2) suggests that TNF-alpha modulates iNOS expression.

PMID:
19802525
DOI:
10.1007/s11010-009-0259-2
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center