Effect of Selective COX-2 Inhibition on Ulcer Healing

For many years the integrity of the stomach mucosal barrier is thought to be maintained by mucosal prostaglandins (PG) synthesized by COX-1. However, the notion that COX-1 protects the stomach and COX-2 induces inflammation may be over-simplistic. In animal studies, COX-2, but not COX-1, is expressed in experimental gastric ulcer. Inhibition of COX-2 delays ulcer healing, indicating that PG derived from COX-2 contributes to restoring the mucosal barrier \[1\]. Whether this animal observation can be generalized to the human stomach is unknown. To date the biological functions of COX-1 and COX-2 in the healing of human gastric ulcer healing is unclear. Unlike experimental ulcers that only express COX-2, recently we have shown that both COX-1 and COX-2 are up-regulated in human gastric ulcers \[2\]. Furthermore, our preliminary results suggest that inhibition of COX-2 alone may not lead to a clinically significant delay in ulcer healing (refer to progress report). These observations suggest that peptic ulcer healing is more complex in the human stomach - both COX isoforms may be involved in the healing process. Inhibition of COX-2 alone may have less adverse effect than non-selective inhibition of both COX isoforms in ulcer healing. The current study aims to resolve the functional significance of COX-2 in human gastric ulcer from a biological and clinical perspective.