Nuclear factor–kappaB: a main regulator of inflammation and cell survival in endometriosis pathophysiology

González-Ramos, Reinaldo; Defrère, Sylvie; Devoto, Luigi

doi:10.1016/j.fertnstert.2012.06.021

Cited by 115 publications

(76 citation statements)

References 125 publications

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“…[28, 29] Specifically, activation of NF-κB through inhibitor of κB kinase epsilon (IKKε) was shown to be associated with more aggressive behavior in ovarian cancer cell lines [30] and has been associated with aberrant cellular activities in endometriosis, a known risk factor for ovarian cancer. [31]…”

Section: Discussionmentioning

confidence: 99%

Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial

Trabert

Pinto

Hartge

et al. 2014

Gynecologic Oncology

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Objective Pro-inflammatory mechanisms may explain the increased ovarian cancer risk linked to more lifetime ovulations, endometriosis, and exposure to talc and asbestos, as well as decreased risk with non-steroidal antiinflammatory drugs. Limited data are available to estimate ovarian cancer risk associated with levels of circulating inflammatory markers. Methods We conducted a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Pre-diagnostic serum levels of 46 inflammation-related biomarkers (11 with a priori hypotheses; 35 agnostic) were measured in 149 incident ovarian cancer cases and 149 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression and adjusted for identified covariates. Results Increased ovarian cancer risk was associated with elevated levels of C-reactive protein (CRP) [tertile (T)3 vs. T1: OR (95% CI) 2.04 (1.06-3.93), p-trend=0.03], interleukin (IL)-1α [detectable vs. undetectable: 2.23 (1.14-4.34)] and tumor necrosis factor alpha (TNF-α) [T3 vs. T1: 2.21 (1.06-4.63), p-trend=0.04] Elevated IL-8 was non-significantly associated with risk [T3 vs. T1: 1.86 (0.96-3.61), p-trend=0.05] In analyses restricted to serous ovarian cancer (n=83), the associations with CRP and IL-8 remained or strengthened [CRP T3 vs. T1: 3.96 (1.14-11.14), p-trend=0.008; IL-8 T3 vs. T1: 3.05 (1.09-8.51), p-trend=0.03]. Elevated levels of CRP and TNF-α remained positively associated with ovarian cancer risk in analysis restricted to specimens collected at least 5 years before diagnosis (n=56). Conclusion These results suggest that CRP, IL-1α, IL-8, and TNF-α are associated with increased risk of subsequently developing ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial

Trabert

Pinto

Hartge

et al. 2014

Gynecologic Oncology

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“…Progesterone exhibits anti-inflammatory activity, and in normal circumstances, an inflammatory response occurs after progesterone withdrawal in the late secretory phase of the menstrual cycle. Decreased progesterone leads to decreased prostaglandin metabolism and increased ROS, which activate an NFκB-mediated inflammatory cascade that induces the processes required for menstruation [82]. The progesterone resistance that characterizes endometriosis mimics this late secretory phase, leading to premature initiation of inflammation [71].…”

Section: Chronic Niche Inflammation In Endometriosis Developmentmentioning

confidence: 99%

Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies

Lin

Chen

Chang

et al. 2018

IJMS

136

104

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Endometriosis is an estrogen-dependent inflammatory disease that affects up to 10% of women of reproductive age and accounts for up to 50% of female infertility cases. It has been highly associated with poorer outcomes of assisted reproductive technology (ART), including decreased oocyte retrieval, lower implantation, and pregnancy rates. A better understanding of the pathogenesis of endometriosis-associated infertility is crucial for improving infertility treatment outcomes. Current theories regarding how endometriosis reduces fertility include anatomical distortion, ovulatory dysfunction, and niche inflammation-associated peritoneal or implantation defects. This review will survey the latest evidence on the role of inflammatory niche in the peritoneal cavity, ovaries, and uterus of endometriosis patients. Nonhormone treatment strategies that target these inflammation processes are also included. Furthermore, mesenchymal stem cell-based therapies are highlighted for potential endometriosis treatment because of their immunomodulatory effects and tropism toward inflamed lesion foci. Potential applications of stem cell therapy in treatment of endometriosis-associated infertility in particular for safety and efficacy are discussed.

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“…3, B and C), supporting the anti-inflammatory effects of the ligands. Another hallmark of endometriosis-associated inflammation is NFκB activation (20). NFκB activity observed by nuclear staining of its subunit p65 was greatly reduced in cells from OBHS- or CLI-treated ectopic lesions (Fig.…”

Section: Resultsmentioning

confidence: 99%

Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis

et al. 2015

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Estrogenic and inflammatory components play key roles in a broad range of diseases including endometriosis, a common estrogen-dependent gynecological disorder in which endometrial tissue creates inflammatory lesions at extrauterine sites, causing pelvic pain and reduced fertility. Current medical therapies focus primarily on reducing systemic levels of estrogens, but these are of limited effectiveness and have considerable side effects. We developed estrogen receptor (ER) ligands, chloroindazole (CLI) and oxabicycloheptene sulfonate (OBHS), which showed strong ER-dependent anti-inflammatory activity in a preclinical model of endometriosis that recapitulates the estrogen dependence and inflammatory responses of the disease in immunocompetent mice and in primary human endometriotic stromal cells in culture. Estrogen-dependent phenomena, including cell proliferation, cyst formation, vascularization, and lesion growth, were all arrested by CLI or OBHS, which prevented lesion expansion and also elicited regression of established lesions, suppressed inflammation, angiogenesis, and neurogenesis in the lesions, and interrupted crosstalk between lesion cells and infiltrating macrophages. Studies in ERα or ERβ knockout mice indicated that ERα is the major mediator of OBHS effectiveness and ERβ is dominant in CLI actions, implying involvement of both ERs in endometriosis. Neither ligand altered estrous cycling or fertility at doses that were effective for suppression of endometriosis. Hence, CLI and OBHS are able to restrain endometriosis by dual suppression of the estrogen-inflammatory axis. Our findings suggest that these compounds have the desired characteristics of preventive and therapeutic agents for clinical endometriosis and possibly other estrogen-driven and inflammation-promoted disorders.

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Nuclear factor–kappaB: a main regulator of inflammation and cell survival in endometriosis pathophysiology

Cited by 115 publications

References 125 publications

Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial

Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial

Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies

Dual suppression of estrogenic and inflammatory activities for targeting of endometriosis

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