| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
RESEARCH COMMUNICATION |
Vascular Inflammation and
a Experimental Pathology, The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, U.K.; and
b Unit of Critical Care Medicine, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, U.K.
Prostanoids produced via the action of cyclo-oxygenase-2 (COX-2) appear central to many inflammatory conditions. Here we show in LPS-treated rats, however, that COX-2 induction alone does not greatly increase prostanoid production in vivo. For this, a second, arachidonic acid liberating stimulus is also required. Thus, only after intravenous injection of bradykinin or exogenous arachidonic acid was a marked increase in prostanoid formation seen. There is, therefore, synergy between proinflammatory mediators: both induction of COX-2 protein and an increase in the supply of arachidonic acid are required to greatly enhance prostanoid production. Second, we show that supplying arachidonic acid to increase prostanoid production reduces the effectiveness of both currently used nonsteroidal antiinflammatory drugs (NSAIDs) (diclofenac) and novel COX-2-selective inhibitors (NS-398, celecoxib) as inhibitors of COX-2 activity. Our data lead to two important conclusions. First, increased prostanoid production in inflammation is a two-component response: increased COX-2 expression and increased arachidonic acid supply. Second, the supply of arachidonic acid to COX-2 determines the effectiveness of NSAIDs. NSAIDs and selective COX-2 inhibitors, therefore, will generally be less effective at more inflamed sites, providing a rationale for the very high doses of NSAIDs required in human conditions such as rheumatoid arthritis.—Hamilton, L. C., Tomlinson, A. M., Mitchell, J. A., Warner, T. D. Synergy between cyclo-oxygenase-2 induction and arachidonic acid supply in vivo: consequences for nonsteroidal antiinflammatory drug efficacy.
Key Words: antiinflammatory agents • cyclooxygenase inhibitors • disease models • prostaglandins • prostaglandin endoperoxide synthase
This article has been cited by other articles:
|
|
 |
|
  E. Fosslien Cardiovascular Complications of Non-Steroidal Anti-Inflammatory Drugs Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 347 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Damirin, H. Tomura, M. Komachi, M. Tobo, K. Sato, C. Mogi, H. Nochi, K. Tamoto, and F. Okajima Sphingosine 1-Phosphate Receptors Mediate the Lipid-Induced cAMP Accumulation through Cyclooxygenase-2/Prostaglandin I2 Pathway in Human Coronary Artery Smooth Muscle Cells Mol. Pharmacol., April 1, 2005; 67(4): 1177 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Benatti, G. Peluso, R. Nicolai, and M. Calvani Polyunsaturated Fatty Acids: Biochemical, Nutritional and Epigenetic Properties J. Am. Coll. Nutr., August 1, 2004; 23(4): 281 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yasumaru, S. Tsuji, M. Tsujii, T. Irie, M. Komori, A. Kimura, T. Nishida, Y. Kakiuchi, N. Kawai, H. Murata, et al. Inhibition of Angiotensin II Activity Enhanced the Antitumor Effect of Cyclooxygenase-2 Inhibitors via Insulin-Like Growth Factor I Receptor Pathway Cancer Res., October 15, 2003; 63(20): 6726 - 6734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Giuliano and T. D. Warner Origins of Prostaglandin E2: Involvements of Cyclooxygenase (COX)-1 and COX-2 in Human and Rat Systems J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 1001 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Calatayud, E. Garcia-Zaragoza, C. Hernandez, E. Quintana, V. Felipo, J. V. Esplugues, and M. D. Barrachina Downregulation of nNOS and synthesis of PGs associated with endotoxin-induced delay in gastric emptying Am J Physiol Gastrointest Liver Physiol, December 1, 2002; 283(6): G1360 - G1367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Bradbury, R. Newton, Y.-M. Zhu, J. Stocks, L. Corbett, E. D. Holland, L. H. Pang, and A. J. Knox Effect of bradykinin, TGF-beta 1, IL-1beta , and hypoxia on COX-2 expression in pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L717 - L725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Giuliano, J. A. Mitchell, and T. D. Warner Sodium Salicylate Inhibits Prostaglandin Formation without Affecting the Induction of Cyclooxygenase-2 by Bacterial Lipopolysaccharide in Vivo J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 894 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Schuster, J. K. Kozlowski, T. McCarthy, J. Morrow, and A. Stephenson Effect of endotoxin on oleic acid lung injury does not depend on priming J Appl Physiol, November 1, 2001; 91(5): 2047 - 2054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F HALTER, A S TARNAWSKI, A SCHMASSMANN, and B M PESKAR Cyclooxygenase 2{---}implications on maintenance of gastric mucosal integrity and ulcer healing: controversial issues and perspectives Gut, September 1, 2001; 49(3): 443 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Ostrom, C. Gregorian, R. M. Drenan, K. Gabot, B. K. Rana, and P. A. Insel Key role for constitutive cyclooxygenase-2 of MDCK cells in basal signaling and response to released ATP Am J Physiol Cell Physiol, August 1, 2001; 281(2): C524 - C531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Watkins, Y. Li, K. G. D. Allen, W. E. Hoffmann, and M. F. Seifert Dietary Ratio of (n-6)/(n-3) Polyunsaturated Fatty Acids Alters the Fatty Acid Composition of Bone Compartments and Biomarkers of Bone Formation in Rats J. Nutr., September 1, 2000; 130(9): 2274 - 2284. [Abstract] [Full Text]
|
|
|
|
|
|
B. A. Watkins and M. F. Seifert Conjugated Linoleic Acid and Bone Biology J. Am. Coll. Nutr., August 1, 2000; 19(4): 478S - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mietus-Snyder, M. S. Gowri, and R. E. Pitas Class A Scavenger Receptor Up-regulation in Smooth Muscle Cells by Oxidized Low Density Lipoprotein. ENHANCEMENT BY CALCIUM FLUX AND CONCURRENT CYCLOOXYGENASE-2 UP-REGULATION J. Biol. Chem., June 2, 2000; 275(23): 17661 - 17670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. K. MacNaughton and K. Cushing Role of Constitutive Cyclooxygenase-2 in Prostaglandin-Dependent Secretion in Mouse Colon In Vitro J. Pharmacol. Exp. Ther., May 1, 2000; 293(2): 539 - 544. [Abstract] [Full Text]
|
|
|
|
|
|
M. B. H. Petrik, M. F. McEntee, C.-H. Chiu, and J. Whelan Antagonism of Arachidonic Acid Is Linked to the Antitumorigenic Effect of Dietary Eicosapentaenoic Acid in ApcMin/+ Mice J. Nutr., May 1, 2000; 130(5): 1153 - 1158. [Abstract] [Full Text]
|
|
|
|
|
|
C.-J. Yuan, A. K. Mandal, Z. Zhang, and A. B. Mukherjee Transcriptional Regulation of Cyclooxygenase-2 Gene Expression: Novel Effects of Nonsteroidal Anti-Inflammatory Drugs Cancer Res., February 1, 2000; 60(4): 1084 - 1091. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. D. Warner, F. Giuliano, I. Vojnovic, A. Bukasa, J. A. Mitchell, and J. R. Vane Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: A full in vitro analysis PNAS, June 22, 1999; 96(13): 7563 - 7568. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
