Suppression of matrix metalloproteinase-9 by prostaglandin E(2) in peritoneal macrophage is associated with severity of endometriosis

• Published in: The American journal of pathology Vol. 167; no. 4; p. 1061
• 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: United States 01.10.2005
• Subjects: Ascitic Fluid - chemistry; Blotting, Western; Case-Control Studies; Cells, Cultured; Dinoprostone - metabolism; Dinoprostone - pharmacology; Endometriosis - enzymology; Endometriosis - pathology; Female; Gene Expression Regulation, Enzymologic - drug effects; Humans; Interferon-gamma - pharmacology; Interleukin-1 - pharmacology; Macrophages, Peritoneal - enzymology; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase Inhibitors; Models, Biological; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index
• ISSN: 0002-9440

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.