Prostaglandin E2 Production and Cyclooxygenase-2 Induction in Human Urinary Tract Infections and Bladder Cancer

Abstract

Increased prostaglandin production correlates positively with cancer risk and cyclooxygenase (COX)-2, the inducible rate limiting enzyme for prostaglandin synthesis, is elevated in bladder cancer cases. Urinary prostaglandin levels and COX-2 expression in urine particulates may increase in urogenital cancer, including bladder cancer, and with infectious and inflammatory processes, including urinary tract infections and that resulting from bacillus Calmette-Guerin (BCG) treatment for bladder cancer. Urinary prostaglandin E2 levels were measured in patients with a urinary tract infection before and after treatment, urogenital cancer (including bladder cancer), bladder cancer in remission and bladder cancer with BCG treatment. COX-1 and COX-2 mRNA and protein were assessed in the human ureter, in normal human bladder muscle and urothelium, and in urine particulates from patients with urinary tract infections, bladder cancer and bladder cancer with BCG treatment. COX-1 protein, and mRNA and COX-2 mRNA were expressed in the ureter, and bladder muscle and urothelium. Urinary prostaglandin E2 levels and COX-2 protein expression in urine particulates were elevated in patients with urinary tract infections and with bladder cancer compared with age matched controls. Successful treatment for urinary tract infections and bladder cancer lowers urinary prostaglandin E2 levels. Urinary prostaglandin E2 and COX-2 protein levels are elevated during BCG treatment. Increased urinary prostaglandin E2 production and COX-2 protein expression correlate with urogenital cancer, urinary tract infections and inflammatory processes, such as those induced by BCG. Patients in whom urinary tract infection was treated with antibiotics or in whom bladder cancer is in remission have reduced urinary prostaglandin E2 compared with those who have active disease.