Cyclooxygenase-2-mediated angiogenesis in carrageenin-induced granulation tissue in rats

A. K. Ghosh, N. Hirasawa, H. Niki, K. Ohuchi

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

The possible participation of cyclooxygenase (COX)-2 in angiogenesis in granulation tissue was analyzed using an air pouch-type carrageenin-induced inflammation model in rats. Injection of carrageenin solution into an air pouch induced gradual increases in the pouch fluid volume and granulation tissue weight as well as angiogenesis in granulation tissue. NS-398 (10-100 μg) inhibited all of these parameters in a dose-dependent manner. NS-398 (100 μg), indomethacin (100 μg), and dexamethasone (10 μg) markedly reduced prostaglandin (PG) E2 levels in the pouch fluid at day 6. NS-398 and indomethacin did not affect protein levels of COX-1 and COX-2 but dexamethasone significantly reduced the level of COX-2 in granulation tissue at day 6. Protein levels of vascular endothelial growth factor (VEGF) in granulation tissue and in the pouch fluid were higher at day 6 than at day 3, and the levels were decreased by treatment with NS-398 (10-100 μg) in a dose-dependent manner. The inhibitory effects of NS-398 (100 μg) were almost the same as those of indomethacin (100 μg). Dexamethasone (10 μg) also reduced VEGF protein levels in granulation tissue at day 6. To clarify the role of PGE2 in VEGF production, minced granulation tissue obtained 3 days after carrageenin injection from the indomethacin-treated rats was incubated in the presence of various concentrations of PGE2. It was shown that VEGF mRNA and protein levels in the minced granulation tissue were increased by PGE2 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.

Original languageEnglish
Pages (from-to)802-809
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume295
Issue number2
Publication statusPublished - 2000 Jan 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Cyclooxygenase-2-mediated angiogenesis in carrageenin-induced granulation tissue in rats'. Together they form a unique fingerprint.

  • Cite this