title: Suppression of matrix metalloproteinase-9 by prostaglandin E(2) in peritoneal macrophage is associated with severity of endometriosis.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China.
authors.forename: Meng-Hsing
authors.initials: MH
authors.lastname: Wu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shoji
authors.forename: Meng-Chi
authors.initials: MC
authors.lastname: Wu
authors.forename: Pei-Chin
authors.initials: PC
authors.lastname: Chuang
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Lin
authors.forename: Mei-Feng
authors.initials: MF
authors.lastname: Huang
authors.forename: Shaw-Jenq
authors.initials: SJ
authors.lastname: Tsai
mesh_terms: D001202:Ascitic Fluid / Q000737:chemistry; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D004715:Endometriosis / Q000201:enzymology* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000201:enzymology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008954:Models, Biological; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: D007375:Interleukin-1; D061965:Matrix Metalloproteinase Inhibitors; D007371:Interferon-gamma; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone