title: Distinct mechanisms regulate cyclooxygenase-1 and -2 in peritoneal macrophages of women with and without endometriosis.
abstract: Prostaglandin (PG) E2 has been shown to stimulate steroidogenesis in ectopic endometriotic stromal cells and may be involved in the development of endometriosis since this disorder is highly estrogen dependent. The biosynthesis of PGE2 is controlled by the rate-limiting enzyme termed cyclooxygenase (COX). The objective of the current study was to investigate the expression of COX in peritoneal macrophages isolated from women with and without endometriosis, and to explore the effects of pro-inflammatory agents on COX expression in peritoneal macrophages. Using quantitative RT-PCR and Western blot analyses, we found that expression of COX-2 was markedly increased (P < 0.05) in peritoneal macrophages isolated from women with early or severe endometriosis, whereas expression of COX-1 was elevated only in the severe stage (P < 0.05). On the contrary, monocytes/macrophages purified from peripheral blood of patients with endometriosis had minimal or undetectable levels of COX-2, and this was not different from disease-free women. Treatment with interleukin-1beta, tumour necrosis factor-alpha or PGE2 caused a significant increase in COX-2 (P < 0.05) but not COX-1 expression in peritoneal macrophages isolated from disease-free women. In contrast, these agents had no substantial effect on COX-1 and COX-2 expression in peritoneal macrophages from women with endometriosis. In summary, expression of COX in peritoneal macrophages was associated with the severity of endometriosis. Elevated expression of both COX-1 and COX-2 in peritoneal macrophages may contribute to the increased peritoneal fluid PGE2 concentrations and may thus play an important role in the development of endometriosis.
authors.affiliation: Institute of Clinical Medicine, Department of Obstetrics/Gynecology, National Cheng Kung University Medical College, Tainan 701, Taiwan, Republic of China.
authors.forename: Meng-Hsing
authors.initials: MH
authors.lastname: Wu
authors.forename: H Sunny
authors.initials: HS
authors.lastname: Sun
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Lin
authors.forename: Kuei-Yang
authors.initials: KY
authors.lastname: Hsiao
authors.forename: Pei-Chin
authors.initials: PC
authors.lastname: Chuang
authors.forename: Hsien-An
authors.initials: HA
authors.lastname: Pan
authors.forename: Shaw-Jenq
authors.initials: SJ
authors.lastname: Tsai
mesh_terms: D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D010537:Peritoneum / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone