Molecular and Cellular Biochemistry

, Volume 336, Issue 1, pp 17–24

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

  • Jyotirmoy Nandi
  • Bipin Saud
  • J. Michael Zinkievich
  • Zhong-jin Yang
  • Robert A. Levine
Article

DOI: 10.1007/s11010-009-0259-2

Cite this article as:
Nandi, J., Saud, B., Zinkievich, J.M. et al. Mol Cell Biochem (2010) 336: 17. doi:10.1007/s11010-009-0259-2

Abstract

Multiple mucosal immune factors, such as TNF-α and IL-1β, are thought to be key mediators involved in inflammatory bowel disease. We evaluated the role of the pro-inflammatory cytokine TNF-α 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-α monoclonal antibody (TNF-Ab, IP) 30 min before indomethacin. Group 4 was treated with 1 h hyperbaric oxygenation (HBO2) for 5 days after indomethacin. Rats were sacrificed at 12 h or 4 days after final indomethacin injection. PDE inhibitor, TNF-Ab, or HBO2 treatment significantly decreased indomethacin-induced ulceration, myeloperoxidase activity, and disease activity index. Although indomethacin significantly increased serum TNF-α and nitrate/nitrite (NOx) concentrations above control values at 12 h, inducible NOS (iNOS) expression was detected only at day 4. Serum IL-1β 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 HBO2 significantly reduced serum/tissue TNF-α, IL-1β, NOx, and iNOS expression. Our data show TNF-α plays an early pro-inflammatory role in indomethacin-induced jejunoileitis. Additionally, down-regulation of NOx by PDE inhibitors, TNF-Ab, or HBO2 suggests that TNF-α modulates iNOS expression.

Keywords

Anti-TNF-α antibodyPhosphodiesterase inhibitorHyperbaric oxygenationIntestinal ulcerationNitric oxideIL-1β

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Jyotirmoy Nandi
    • 1
  • Bipin Saud
    • 1
  • J. Michael Zinkievich
    • 1
  • Zhong-jin Yang
    • 2
  • Robert A. Levine
    • 1
  1. 1.Division of Gastroenterology, Department of MedicineState University of New York, Upstate Medical UniversitySyracuseUSA
  2. 2.Department of AnesthesiologyState University of New York, Upstate Medical UniversitySyracuseUSA