Suppression of Matrix Metalloproteinase-9 by Prostaglandin E2 in Peritoneal Macrophage Is Associated with Severity of Endometriosis

• Published in: The American journal of pathology Vol. 167; no. 4; pp. 1061 - 1069
• Main Authors: Wu, Meng-Hsing, Shoji, Yutaka, Wu, Meng-Chi, Chuang, Pei-Chin, Lin, Chen-Chung, Huang, Mei-Feng, Tsai, Shaw-Jenq
• Format: Journal Article
• Language: English
• Published: ASIP 01.10.2005; American Society for Investigative Pathology
• Subjects: Original Research Paper
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)61195-9

Decreased phagocytotic ability of macrophages has been reported to be associated with the severity of endometriosis, although the underlying mechanism remains uncharacterized. Expression and secretion of matrix metalloproteinase (MMP)-9 by macrophages is a means to degrade the extracellular matrix of cells that are designated for phagocytosis. Here, we describe the regulation of MMP-9 expression and activity in peritoneal macrophages of women with endometriosis. Results demonstrated that peritoneal macrophages isolated from women with endometriosis have decreased levels of protein and enzyme activity of MMP-9. Treatment of macrophages with peritoneal fluid obtained from patients with severe endometriosis inhibited MMP-9 expression and gelatinase activity. Further investigation identified prostaglandin (PG) E 2 as the major factor in the peritoneal fluid that inhibited MMP-9 activity. The inhibitory effect of PGE 2 was mediated via the EP2/EP4-dependent PKA pathway. Furthermore, expression of tissue inhibitor of metalloproteinase-1, tissue inhibitor of metalloproteinase-2, and RECK in macrophages was not affected by treatment with PGE 2 , indicating the effect of PGE 2 on suppressing MMP-9 activity was not mediated by up-regulation of its inhibitor. Our results suggest that decreased phagocytotic capability of peritoneal macrophage in patients with endometriosis may be caused by PGE 2 -mediated decreases in MMP-9 expression.