Abstract
The possible participation of prostaglandin (PG) E2 in angiogenesis in the granulation tissue was analyzed using an air pouch-type carrageenin-induced inflammation model in rats. Injection of carrageenin solution into a pre-formed air pouch on the dorsum induced the increase in the pouch fluid volume, the granulation tissue formation and the angiogenesis in the granulation tissue. The cyclooxygenase (COX) -2 inhibitor NS-398 as well as the COX-1/COX-2 inhibitor indomethacin inhibited all of these parameters, suggesting that COX-2 plays a role in angiogenesis in addition to inflammatory responses. The increase in protein levels of vascular endothelial growth factor (VEGF) in the supernatant fraction of the pouch fluid was inhibited by treatment with NS-398 or indomethacin. To clarify the role of PGE2 in VEGF production, the minced granulation tissue was incubated in the presence of various concentrations of PGE2. It was shown that PGE2 (0.01-1 μM) increased VEGF protein levels in the conditioned medium of the minced granulation tissue and VEGF mRNA levels in the minced granulation tissue in a concentration-dependent manner. These findings suggest that COX-2-derived PGE2 plays a significant role in angiogenesis in the carrageenin-induced granulation tissue through VEGF formation. The mechanism by which PGE2 induces VEGF production is discussed.
