Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis

Pirdel, Leila; Pirdel, Manijeh

doi:10.1530/rep-13-0552

Cited by 45 publications

(25 citation statements)

References 114 publications

(122 reference statements)

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“…17, 18, 19, 20 The co-culture with ESCs led to a threefold upregulation of IL-27 + monocytes (Figure 3a). In addition, LPS stimulation significantly increased IL-27 levels in monocytes (Figure 3b).…”

Section: Resultsmentioning

confidence: 99%

IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis

et al. 2017

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Endometriosis is an estrogen-dependent inflammatory disease. The anti-inflammatory cytokine IL-10 is also increased in endometriosis. IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. However, the mechanism of inducing IL-10-producing Th17 cells is still largely unknown. The present study investigated the differentiation mechanism and role of IL-10-producing Th17 cells in endometriosis. Here, we report that IL-10+Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis, along with an elevation of IL-27, IL-6 and TGF-β. Compared with peripheral CD4+ T cells, endometrial CD4+ T cells highly expressed IL-27 receptors, especially the ectopic endometrium. Under external (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and local (estrogen, IL-6 and TGF-β) environmental regulation, IL-27 from macrophages and endometrial stromal cells (ESCs) induces IL-10 production in Th17 cells in vitro and in vivo. This process may be mediated through the interaction between c-musculoaponeurotic fibrosarconna (c-Maf) and retinoic acid-related orphan receptor gamma t (RORγt), and associated with the upregulation of downstream B lymphocyte-induced maturation protein-1 (Blimp-1). IL-10+Th17 cells, in turn, stimulate the proliferation and implantation of ectopic lesions and accelerate the progression of endometriosis. These results suggest that IL-27 is a pivotal regulator in endometriotic immune tolerance by triggering Th17 cells to produce IL-10 and promoting the rapid growth and implantation of ectopic lesions. This finding provides a scientific basis for potential therapeutic strategies aimed at preventing the development of endometriosis, especially for patients with high levels of IL-10+Th17 cells.

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Section: Resultsmentioning

confidence: 99%

IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis

et al. 2017

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“…An increasing number of studies have focused on the importance of immunological imbalances in women with endometriosis. It has been confirmed that, a permissive peritoneal environment may be associated with the initiation and development of endometriosis (1)(2)(3)11). Rather than effectively removing the retrograde endometrial fragments in the pelvic cavity, the tolerant environment facilitates the implantation, neo-angiogenesis and proliferation of ectopic endometrial tissue (15,16).…”

Section: Discussionmentioning

confidence: 95%

“…Inflammation of the surrounding pelvic microenvironment is thought to have an important role in the initiation and progression of endometriosis, in addition to ovarian steroid hormones (1). The ectopic growth of 'lesions', consisting of endometrial cells outside the uterine cavity, stimulate an inflammatory response, which initiates the activation of macrophages and leads to increased concentrations of cytokines and growth factors in the peritoneal fluid (2,3). Indoleamine 2,3-dioxygenase (IDO1) is an intracellular heme enzyme that catalyzes the initial and rate-limiting step in the metabolism of the essential amino acid tryptophan in the kynurenine pathway.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive macrophages induced by IDO1 promote the growth of endometrial stromal cells in endometriosis

Mei

Chang

Sun

2017

Molecular Medicine Reports

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It was previously demonstrated that anomalous expression of indoleamine 2,3-dioxygenase-1 (IDO1) in endometrial stromal cells (ESCs) stimulated an inflammatory response that subsequently initiated the activation of immunosuppressive macrophages in endometriosis. The aim of the present study was to clarify the effect of IDO1‑induced macrophages on the growth of ESCs in endometriosis. Normal ESCs, ectopic ESCs and normal ESCs treated with plasmid pEGFP‑N1‑IDO1 or SD11‑IDO1 short hairpin RNA were co‑cultured with peripheral blood‑derived monocyte (PBMC)‑driven macrophages directly for 48 h. Compared with normal ESCs, the PBMC‑driven macrophages that were co‑cultured with ectopic ESCs displayed a lower phagocytic ability. pEGFP‑N1‑IDO1 transfection of normal ESCs also decreased the phagocytic ability of co‑cultured macrophages. Additionally, pEGFP‑N1‑IDO1‑transfected ESC‑induced macrophages significantly increased the viability and proliferation of ESCs, while ESC apoptosis was decreased, compared with control ESCs. In conclusion, IDO1 educated-macrophages may facilitate the survival of retrograde endometrial tissues, and be involved in the pathogenesis of endometriosis.

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“…However, these theories remain controversial. 2,3 Endometriosis develops in 5% to 10% of women of reproductive age, 4 and in Cipto Mangunkusumo Hospital (CMH), Jakarta, in 2010, endometriosis accounted for 42.62% of all benign gynecologic abnormalities. 5 The clinical manifestations are varied and range from no symptoms to debilitating pain in about 40% to 60% of patients with endometriosis-associated dysmenorrhea.…”

Section: Introductionmentioning

confidence: 99%

Expression is Down-Regulated by Oxidative Stress in Endometriosis and Endometriosis-Associated Ovarian Cancer

2017

Translational Oncogenomics

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Oxidative stress is considered an important factor in the development of endometriosis, including its malignant transformation. Previous studies have found that AT-rich interactive domain 1A (ARID1A), a tumor suppressor gene, is frequently mutated and inactivated in endometriosis-associated ovarian cancer (EAOC), and such a change in this gene is considered an early event in malignant transformation. We observed oxidative stress status by measuring the activity of the antioxidant enzyme manganese superoxide dismutase (MnSOD), malondialdehyde (MDA), and ARID1A gene expression in tissue samples from patients with endometriosis, EAOC, or non-endometriosisassociated ovarian cancer (non-EAOC). We also induced oxidative stress in the cultured cells from patients with primary endometriosis by adding H 2 O 2 and tested for any alteration of ARID1A gene expression based on different H 2 O 2 concentrations. The results showed that MnSOD activity in endometriosis and EAOC was lower than in non-EAOC, but MDA levels were higher. This study also showed that oxidative stress reduced ARID1A gene expression.

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Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis

Cited by 45 publications

References 114 publications

IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis

IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis

Immunosuppressive macrophages induced by IDO1 promote the growth of endometrial stromal cells in endometriosis

Expression is Down-Regulated by Oxidative Stress in Endometriosis and Endometriosis-Associated Ovarian Cancer

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