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

Meng-Hsing Wu, Wu MH, Meng‐Hsing Wu, Yutaka Shoji, Shoji Y, Wu MC, Meng‐Chi Wu, Meng-Chi Wu, Chuang PC, Pei-Chin Chuang, Pei‐Chin Chuang, Lin CC, Chen-Chung Lin, Mei-Feng Huang, Huang MF, Mei‐Feng Huang, Shaw-Jenq Tsai, Shaw‐Jenq Tsai
The American Journal of Pathology · 2005 · vol. 167(4) , pp. 1061–1069 · doi:10.1016/s0002-9440(10)61195-9 · PMID:16192641 · PMC1603672 · W2029035194
article OA: bronze CC0 ⤵ 72 in-corpus citations
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Prostaglandin E2 suppresses matrix metalloproteinase-9 in peritoneal macrophages, a process linked to the severity of endometriosis.

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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.

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Condition tags

endometriosis

MeSH descriptors

Dinoprostone Endometriosis Macrophages, Peritoneal Matrix Metalloproteinase Inhibitors Severity of Illness Index Ascitic Fluid Ascitic Fluid Blotting, Western Case-Control Studies Cells, Cultured Dinoprostone Dinoprostone Endometriosis Endometriosis Female Gene Expression Regulation, Enzymologic Gene Expression Regulation, Enzymologic Humans Interferon-gamma Interferon-gamma

Funding

funders
[{'doi': '10.13039/501100001868', 'name': 'National Science Council', 'awards': ['NSC-92-2312-B-006-019']}, {'doi': '10.13039/501100001868', 'name': 'National Science Council', 'awards': ['NSC-92-2314-B-006-050']}]

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References (89)

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