Vol. 18, No. 6, 2009
Issue release date: October 2009
Open Access Gateway
Med Princ Pract 2009;18:477–481
(DOI:10.1159/000235898)
Original Paper
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Cross-Talk between Inducible Nitric Oxide Synthase and Cyclooxygenase in Helicobacter-pylori-Induced Gastritis

Franco L.a · Talamini G.b
aSection of Pharmacology, Department of Medicine and Public Health, and bDepartment of Surgical and Gastroenterological Sciences, University of Verona, Verona, Italy
email Corresponding Author


 goto top of outline Key Words

  • Helicobacter pylori
  • Inducible nitric oxide synthase
  • Cyclooxygenase 2
  • Gastric mucosa
  • Nitric oxide
  • Prostaglandin

 goto top of outline Abstract

Objectives: The present study examined the cross-talk between prostanoids and nitric oxide (NO) in human gastric biopsies during Helicobacter pylori infection. Subjects and Methods: A pool of 1 or 2 biopsies per patient (11 H. pylori positive and 9 H. pylori negative) were incubated in the medium with/without drugs, 1400W and NS-398, inhibitors of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), respectively. Levels of NO and prostaglandin E2 (PGE2), predominant products of activity of NOS and COX enzymes, were measured in the medium whereas the expressions of iNOS and COX protein, examined by Western blotting, were measured in the biopsies. Results: The 11 patients with H. pylori infection showed a marked expression of COX-2 and iNOS proteins and high levels of PGE2 and NO, as a consequence of iNOS and COX-2 activation, while proteins were absent and the level of nitrite and PGE2 was low in the 9 noninfected patients. The COX-2 inhibitor decreased both NO and PGE2. The iNOS-specific inhibitor decreased NO but did not have any effect on the increase in gastric mucosal PGE2. Both inhibitors had no effect on the protein level of these two enzymes. Conclusions: The data showed that COX-2 inhibitor might modulate the iNOS pathway, suggesting that COX-2 activity and/or its products may be related to the functional activation of iNOS but not to the expression of iNOS protein.

Copyright © 2009 S. Karger AG, Basel


 goto top of outline References
  1. Tsutsumi S, Tomisato W, Takano T, Rokutan K, Tsuchiya T, Mizushima T: Gastric irritants induce apoptosis in guinea pig gastric mucosal cells in primary culture. Biochim Biophys Acta 2002;1589:168–180.
  2. Konturek SJ: The physiological role of prostaglandins in cytoprotection; in Cheli R (ed): Gastric Protection. New York, Raven Press, 1988, p 13.
  3. Whittle BJR, Lopez-Belmonte J, Moncada S: Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat. Br J Pharmacol 1990;99:607–611.
  4. Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 1991;43:109–142.
  5. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van de Putte LB, Lipsky PE: Cyclooxygenase in biology and disease. FASEB J 1998;12:1063–1073.
  6. Fischer H, Becker JC, Boknik P, Huber V, Lüss H, Neumann J, Schmitz W, Domschke W, Stachura J, Kunturek JW: Expression of constitutive nitric oxide synthase in rat and human gastrointestinal tract. Biochim Biophys Acta 1999;1450:414–422.
  7. Garcia-Vitoria M, Garcia-Corchon C, Rodriguez JA, Garcia-Amigot F, Burrell MA: Expression of neuronal nitric oxide synthase in several types of the rat gastric epithelium. J Histochem Cytochem 2000;48:1111–1119.
  8. Ambs S, Hussain SP, Harris CC: Interactive effects of nitric oxide and the p53 tumor suppressor gene in carcinogenesis and tumor progression. FASEB J 1997;11:443–448.
  9. Brown JF, Tepperman BL, Hanson PJ, Whittle BJR: Lipopolysaccharide induces Ca2+-independent nitric oxide synthase activity in rat gastric mucosal cells. Eur J Pharmacol 1994;292:111–114.
  10. Franco L, Doria D: Nitric oxide enhances prostaglandin production in ethanol-induced gastric mucosal injury in rats. Eur J Pharmacol 1998;348:247–256.
  11. Boughton-Smith NK, Evans SM, Laszlo F, Whittle BJR, Moncada S: The induction of nitric oxide synthase and intestinal vascular permeability by endotoxin in the rat. Br J Pharmacol 1993;110:1189–1195.
  12. Tepperman BL, Soper BD: Nitric oxide synthase induction and cytoprotection of rat gastric mucosa from injury by ethanol. Can J Physiol Pharmacol 1994;72:1308–1312.
  13. Wallace JL, Miller MJ: Nitric oxide in mucosal defense: a little goes a long way. Gastroenterology 2000;119:512–520.
  14. Parsonnet J, Hansen S, Rodriguez L, Gelb AB, Warnke RA, Jellum E, Orentreich N, Vogelman JH, Friedmam GD: Helicobacter pylori infection and gastric lymphoma. N Engl J Med 1994;330:1267–1271.
  15. Mannick EE, Bravo LE, Zarama G, Realpe JL, Zhang XJ, Ruiz B, Fontham ETH, Mera R, Miller MJS, Correa P: Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants. Cancer Res 1996;56:3238–3243.
  16. Dixon MF, Genta MG, Yardley JH, Pelay C: Classification and grading of gastritis. Am J Surg Pathol 1996;20:1161–1181.
  17. Enzyme immunoassay prostaglandin E metabolite EIA kit. Ann Arbor, Cayman Chemical Company, 2004.
  18. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantitites of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–254.
  19. Franco L, Talamini G, Carra G, Doria D: Expression of COX-1, COX-2, and inducible nitric oxide synthase protein in human gastric antrum with Helicobacterpylori infection. Prostaglandins Other Lipid Mediat 1999;58:9–17.
  20. Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, Lee SS: Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 2001;480–481:243–268.
  21. Beyaert R (ed): Nuclear Factor κB: Regulation and Role in Disease. Dordrecht, Kluwer Academic Publishers, 2003.
  22. Goodwing DC, Landino LM, Marnett LJ: Effects of nitric oxide and nitric oxide-derived species on prostaglandin endoperoxide synthase and prostaglandin biosynthesis. FASEB J 1999;13:1121–1136.

 goto top of outline Author Contacts

Dr. Luigina Franco
Department of Medicine and Public Health, Section of Pharmacology
University of Verona, Policlinico G. Rossi, P.le L.A. Scuro 10
IT–37134 Verona (Italy)
Tel. +39 045 802 7604, Fax +39 045 802 7452, E-Mail Luigina.Franco@univr.it


 goto top of outline Article Information

Received: July 16, 2008
Revised: January 27, 2009
Published online: September 30, 2009
Number of Print Pages : 5
Number of Figures : 2, Number of Tables : 1, Number of References : 22


 goto top of outline Publication Details

Medical Principles and Practice (International Journal of the Kuwait University Health Sciences Centre)

Vol. 18, No. 6, Year 2009 (Cover Date: October 2009)

Journal Editor: Owunwanne A. (Kuwait)
ISSN: 1011-7571 (Print), eISSN: 1423-0151 (Online)

For additional information: http://www.karger.com/MPP


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