Roles of COX-1 and COX-2 in gastrointestinal pathophysiology.

In this review, COX-1 and COX-2 proteins have been shown to be homologous in protein structure and ability to synthesize PG, but they have been also shown to be induced differently. COX-1 mRNA and protein have been shown to be induced slowly in intestinal crypt cells in response to irradiation and suggested to be important for crypt cell survival. Therefore, the cox-1 gene is suggested to be a delayed response gene in some systems. However, in cox-1 gene knockout animals there are no pathological gastric and intestinal findings. Although the precise roles of COX-1 in epithelial proliferation and differentiation in the gastrointestinal tract are not yet known, it apparently acts as a constitutive PG producer, thereby protecting the mucosa. On the other hand, COX-2 mRNA and protein have been shown to be induced rapidly in inflammatory sites of the stomach and colon. Thus, COX-2-derived PG presumably plays a role in the repair process of gastritis, ulcers, and colitis. Furthermore, loss of apc gene function probably induces COX-2 mRNA in gastrointestinal mucosa. Thus, high expression levels of COX-2 may lead to phenotypic changes in both intestinal epithelial cells and colon cancer cells.