Increased Expression of Cyclooxygenase‐2 in Local Lesions of Endometriosis Patients

Chishima, Fumihisa; Hayakawa, Satoshi; Sakai, Kenji; Kinukawa, Noriko; Aleemuzzaman, Sheike; Nemoto, Norimichi; Yamamoto, Tatsuo; Honda, Mitsuo

doi:10.1034/j.1600-0897.2002.01101.x

Cited by 137 publications

(83 citation statements)

References 24 publications

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“…It has been reported that COX-2 plays a role in endometriotic cell proliferation, survival, migration and invasion [9,15,16]. Chishima et al [17] showed increased expression of COX-2 in local lesions of endometriosis patients. They put forward that hyperactivation of COX-2 with abnormal PG production contributes to the pathophysiology of endometriosis and disease progression.…”

Section: Discussionmentioning

confidence: 99%

Regression of Experimentally Induced Endometriosis with a New Selective Cyclooxygenase-2 Enzyme Inhibitor

Kilico

Kökçü²,

Kefeli³

et al. 2013

Gynecol Obstet Invest

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Background: Cyclooxygenase-2 (COX-2) levels increase in women with endometriosis. COX-2, via increasing prostaglandin E₂, contributes to an increase in vascular endothelial growth factor. In this way, COX-2 may contribute to the progression and continuity of endometriosis. We investigated the effect of dexketoprofen trometamol, a new selective COX-2 enzyme inhibitor, on experimentally induced endometriotic cysts. Methods: Experimental endometriotic cysts were created in 60 adult female Wistar albino rats. The rats were randomized to 2 equal groups, a control (group Con) and a dexketoprofen (group Dex) group. Six weeks later, cyst volumes were measured as in vivo (volume 1). Following volume 1 measurement, for 4 weeks group Con received 0.1 ml distilled water; group Dex received 0.375 mg dexketoprofen trometamol/0.1 ml distilled water, intramuscularly, twice a day. At the end of administration, the cyst volumes were remeasured (volume 2), and the cysts totally excised and weighed. Glandular (GT) and stromal tissues (ST) and natural killer (NK) cell contents in the cyst wall were scored. Results: NK cell content and volume 1 were not different between the 2 groups. Volume 2, cyst weight, and GT and ST contents in group Dex were significantly lower than those in group Con. Conclusion: Dexketoprofen trometamol significantly reduced the development of experimentally induced endometriotic cysts both macroscopically and microscopically.

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Section: Discussionmentioning

confidence: 99%

Regression of Experimentally Induced Endometriosis with a New Selective Cyclooxygenase-2 Enzyme Inhibitor

Kilico

Kökçü²,

Kefeli³

et al. 2013

Gynecol Obstet Invest

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“…COX-2 is more abundantly expressed in ectopic endometria than in the eutopic endometria during similar phases of the menstrual cycle in women (Ota et al, 2001;Chishima et al, 2002). COX-2 is expressed in both glandular epithelium and stroma of endometriotic tissues in women (Ota et al, 2001;Chishima et al, 2002). Cytokines increase COX-2 expression in endometriotic stromal cells (Wu et al, 2007).…”

Section: Introductionmentioning

confidence: 97%

“…Much of the endometriotic pain is thought to be due to high levels of PGE 2 (Allen et al, 2005). COX-2 is more abundantly expressed in ectopic endometria than in the eutopic endometria during similar phases of the menstrual cycle in women (Ota et al, 2001;Chishima et al, 2002). COX-2 is expressed in both glandular epithelium and stroma of endometriotic tissues in women (Ota et al, 2001;Chishima et al, 2002).…”

Section: Introductionmentioning

confidence: 97%

Hypoxia induces expression of COX-2 through the homeodomain transcription factor CDX1 and orphan nuclear receptor SHP in human endometrial cells

Kim

et al. 2011

MHR: Basic Science of Reproductive Medicine

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Endometriosis, the presence of ectopic endometrial tissue outside the uterine cavity, is a common disease affecting women during their reproductive years. The aim of this study was to identify the molecular mechanism of transcriptional regulation of inflammatory cyclooxygenase-2 (COX-2) gene during endometriosis by hypoxia. Hypoxia induced COX-2 expression in endometrial cells together with the induction of the orphan nuclear receptor SHP and intestinal-specific transcription factor Caudal-related transcription factor 1 (CDX1). Hypoxia-inducible factor (HIF)-1a was responsible for SHP induction mediated by a hypoxia. In addition, we observed that ectopic expression of CDX1 enhanced COX-2 gene expression in hypoxia-dependent fashion. Additionally, we evaluated that induction of CDX1 by hypoxia was mediated by SHP. Expression of COX-2, CDX1, SHP and HIF-1a mRNA in hypoxia-treated human endometrial cells were significantly higher than normal control cells. These results suggest that the SHP and CDX1 expression increased by hypoxia play an active role in inducing inflammatory COX-2 expression in the pathogenesis of endometriosis.

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“…Since PGs are unstable factors with a very short halflife (Ferreira and Vane, 1967), it is believed they must be produced and function locally. Hence, peritoneal macrophages (Wu et al, 2002) and ectopic endometriotic tissue (Ota et al, 2001;Chishima et al, 2002Chishima et al, , 2007 are two of the most likely candidates implicated in raising peritoneal eicosanoid levels.…”

Section: Introductionmentioning

confidence: 99%

Expression of eicosanoid biosynthetic and catabolic enzymes in peritoneal endometriosis

et al. 2009

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background: Increased peritoneal eicosanoid concentrations have been reported in endometriosis patients and might be important in disease-associated pain and inflammation. Here, we evaluated the expression of key biosynthetic and catabolic enzymes involved in this abnormal eicosanoid production in peritoneal macrophages and endometriotic lesions.methods: Peritoneal macrophages, endometriotic lesions and matched eutopic endometrium were collected from endometriosis patients (n ¼ 40). Peritoneal macrophages and eutopic endometrium samples were also collected from disease-free women (n ¼ 25). Expression of type IIA secretory phospholipase A 2 (sPLA 2 -IIA), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and 5-lipoxygenase (5-LO) was quantified by real-time PCR, and these five key enzymes were localized by immunohistochemistry.results: sPLA 2 -IIA, COX-2 and mPGES-1 mRNA was significantly increased in peritoneal macrophages of endometriosis patients compared with controls (P ¼ 0.006, P ¼ 0.016 and P ¼ 0.025, respectively). In endometriosis patients, sPLA 2 -IIA, mPGES-1 and 15-PGDH mRNA was significantly enhanced in peritoneal lesions compared with matched eutopic endometrium (P , 0.001, P , 0.001 and P ¼ 0.005, respectively). In eutopic endometrium, a significant decrease in 15-PGDH mRNA was found in the endometriosis group compared with controls (P ¼ 0.023). Finally, sPLA 2 -IIA, COX-2, mPGES-1 and 15-PGDH immunostaining was found mainly in endometrial glands, whereas 5-LO was distributed throughout the glands and stroma. conclusions: Our study highlights an imbalance between eicosanoid biosynthesis and degradation in endometriosis patients. Both peritoneal macrophages and endometriotic lesions may be involved. Research into new molecules inhibiting biosynthetic enzymes (such as sPLA 2 -IIA and mPGES-1) and/or activating catabolic enzymes (such as 15-PGDH) may prove to be a major field of investigation in the development of targeted medical therapies.

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Increased Expression of Cyclooxygenase‐2 in Local Lesions of Endometriosis Patients

Abstract: Hyper activation of COX-2 with abnormal prostaglandin generation is considered to contribute to the pathophysiology of endometriosis and disease progression.

Cited by 137 publications

References 24 publications

Regression of Experimentally Induced Endometriosis with a New Selective Cyclooxygenase-2 Enzyme Inhibitor

Regression of Experimentally Induced Endometriosis with a New Selective Cyclooxygenase-2 Enzyme Inhibitor

Hypoxia induces expression of COX-2 through the homeodomain transcription factor CDX1 and orphan nuclear receptor SHP in human endometrial cells

Expression of eicosanoid biosynthetic and catabolic enzymes in peritoneal endometriosis

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