Prostaglandin E 2 regulate matrix metalloproteinase‐9 in peritoneal macrophage of patient with endometriosis

Endometriosis is a gynecological disorder that causes the chronic pelvic pain, dysmenorrhea, and infertility in reproductive age women with 10–15% prevalence. Alteration and/or dysfunction of immune system such as poor phagocytotic capacity of peritoneal macrophages in patient with endometriosis has been reported; however, mechanism of suppressed phagocytotic capacity of macrophage is not well known. Expression and secretion of matrix metalloproteinase‐9 (MMP‐9) by macrophage is a mean to degrade the extracellular matrix of cells that are designated for phagocytosis. The study was designed to characterize functional relationship between MMP‐9 levels in peritoneal macrophage and severity of endometriosis. Results revealed that peritoneal macrophage isolated from women with endometriosis has decreased enzyme activity, protein and mRNA of MMP‐9. Treatment with peritoneal fluid obtained from patient with endometriosis but not that from normal women significantly suppressed MMP‐9 expression in peritoneal macrophage. Further study demonstrated that prostaglandin E 2 (PGE 2 ) decreased MMP‐9 activity and protein expression, which was mediated via EP2 and EP4 receptors. In contrast, PGE 2 failed to affect levels of tissue inhibitor of metalloproteinase (TIMP)‐1, TIMP‐2 and RECK in peritoneal macrophage. These results indicated that decreased phagocytotic capability of peritoneal macrophage in patients with endometriosis may be caused by PGE 2 ‐mediated decrease in MMP‐9 expression.