The involvement of multifunctional TGF-β and related cytokines in pathogenesis of endometriosis

Sikora, Justyna; Smycz‐Kubańska, Marta; Mielczarek‐Palacz, Aleksandra; Bednarek, Ilona; Kondera-Anasz, Zdzisława

doi:10.1016/j.imlet.2018.10.011

Cited by 62 publications

(49 citation statements)

References 54 publications

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“…This proinflammatory cytokine has been shown to be involved in autoimmune diseases, mechanical injury, infection, cancer, obesity, and chronic inflammatory disorders (16). In the context of endometriosis, we and others have shown that IL-17A is elevated in the plasma and peritoneal fluid of women with endometriosis compared to controls and that endometriotic lesions produce IL-17 (17,18). T H 17 cells are also elevated in women with endometriosis compared to controls and women in advanced stages of endometriosis have higher numbers of T H 17 cells compared to early stage patients with minimal/mild endometriosis (19)(20)(21).…”

Section: Introductionmentioning

confidence: 91%

IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis

et al. 2020

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Endometriosis is a debilitating gynecological disease characterized by the extrauterine presence of endometrial-like tissues located on the peritoneal membrane and organs of the pelvic cavity. Notably, dysfunctional immune activation in women with endometriosis could also contribute to the development of disease. In particular, alternatively activated (M2) peritoneal macrophages are shown to aid peritoneal lesion development by promoting remodeling of extracellular matrix and neovascularization of lesions. However, the stimuli responsible for polarizing M2 macrophages in endometriosis remain elusive. Interleukin-17A (IL-17A) can induce M2 macrophage polarization in other disease models and IL-17A is elevated in the plasma and endometriotic lesions of women with endometriosis. In this study, we investigated whether IL-17A could induce macrophage recruitment and M2 polarization, while promoting endometriotic lesion growth through enhanced vascularization. By utilizing a co-culture of macrophage-like THP-1 cells with an endometriotic epithelial cell line, our in vitro results suggest that IL-17A indirectly induces M2 markers CCL17 and CD206 by interacting with endometriotic epithelial cells. Further, in a syngeneic mouse model of endometriosis, IL-17A treatment increased macrophages in the peritoneum, which were also M2 in phenotype. However, IL-17A treatment did not augment proliferation or vascularization of the lesion in the study time frame. These findings suggest that IL-17A may be a stimulus inducing the pathogenic polarization of macrophages into the M2 phenotype by first acting on the endometriotic lesion itself.

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Section: Introductionmentioning

confidence: 91%

IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis

et al. 2020

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“…The accumulation of Tregs in the peritoneal cavity may not only be a result of active translocation from the peripheral blood but may also be due to their local induction (153). Higher levels of IL-10 and TGF-β, two key cytokines responsible for regulating the proliferation and activity of Tregs, were found in the peritoneal fluid and serum of patients with endometriosis than in normal controls (164,165). Compared with serum levels, the level of cytokines in peritoneal fluid was significantly higher (165).…”

Section: Endometriosismentioning

confidence: 99%

“…Higher levels of IL-10 and TGF-β, two key cytokines responsible for regulating the proliferation and activity of Tregs, were found in the peritoneal fluid and serum of patients with endometriosis than in normal controls (164,165). Compared with serum levels, the level of cytokines in peritoneal fluid was significantly higher (165). Furthermore, IL-10 and TGF-β mRNA expression were significantly higher in ectopic lesions than eutopic endometrium from women with or without endometriosis, particularly in cases of advanced endometriosis (166).…”

Section: Endometriosismentioning

confidence: 99%

Role of Regulatory T Cells in Regulating Fetal-Maternal Immune Tolerance in Healthy Pregnancies and Reproductive Diseases

2020

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Regulatory T cells (Tregs) are a specialized subset of T lymphocytes that function as suppressive immune cells and inhibit various elements of immune response in vitro and in vivo. While there are constraints on the number or function of Tregs which can be exploited to evoke an effective anti-tumor response, sufficient expansion of Tregs is essential for successful organ transplantation and for promoting tolerance of self and foreign antigens. The immune-suppressive property of Tregs equips this T lymphocyte subpopulation with a pivotal role in the establishment and maintenance of maternal tolerance to fetal alloantigens, which is necessary for successful pregnancy. Elevation in the level of pregnancy-related hormones including estrogen, progesterone and human chorionic gonadotropin promotes the recruitment and expansion of Tregs, directly implicating these cells in the regulation of fetal-maternal immune tolerance. Current studies have provided evidence that a defect in the number or function of Tregs contributes to the etiology of several reproductive diseases, such as recurrent spontaneous abortion, endometriosis, and pre-eclampsia. In this review, we provide insight into the underlying mechanism through which Tregs contribute to pregnancy-related immune tolerance and demonstrate the association between deficiencies in Tregs and the development of reproductive diseases.

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“…For instance, TGF-β1 was found to be upregulated in endometriotic epithelial cells compared with that in normal endometrial cells [18]. TGF-β1 levels have been reported to be significantly elevated in the peritoneal fluid and serum of women with endometriosis, which may create a favorable environment for endometriotic lesion formation [19]. These researches suggested that ectopic expression of TGF-β1 was involved in the pathophysiology of endometriosis.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of vascular cell adhesion molecule 1 impedes transforming growth factor beta 1-mediated proliferation, migration, and invasion of endometriotic cyst stromal cells

Zhang

Lai

et al. 2019

Reprod Biol Endocrinol

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Purpose Endometriosis is one of the most common, difficult, and complicated gynecological disorders. Vascular cell adhesion molecule 1 (VCAM-1) has been reported to be aberrantly expressed in patients with endometriosis. However, the exact role and mechanism of VCAM-1 in endometriosis remains unclear. Methods The expression of transforming growth factor beta 1 (TGF-β1) and VCAM-1 was determined by quantitative real-time polymerase chain reaction and western blotting. Human endometriotic cells were cultured and their responsiveness to TGF-β1 was evaluated by Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, and transwell migration and invasion assays. Results The levels of TGF-β1 and VCAM-1 mRNA were upregulated in the endometriotic tissues. Knockdown of TGF-β1 in endometriotic cyst stromal cells caused a marked inhibition of cell proliferation, migration, and invasion. Treatment of endometriotic cyst stromal cells with TGF-β1 resulted in an obvious promotion of cell proliferation, migration, and invasion, and strikingly increased the protein expression of VCAM-1. Silencing of Smad3 abated TGF-β1-stimulated VCAM-1 expression. Furthermore, the promoting effects of TGF-β1 on the proliferation, migration, and invasion of endometriotic cyst stromal cells were blocked by silencing of VCAM-1. Conclusion Knockdown of VCAM-1 impedes TGF-β1-mediated proliferation, migration, and invasion of endometrial cells, thereby indicating that VCAM-1 may serve as a therapeutic target for endometriosis.

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The involvement of multifunctional TGF-β and related cytokines in pathogenesis of endometriosis

Cited by 62 publications

References 54 publications

IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis

IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis

Role of Regulatory T Cells in Regulating Fetal-Maternal Immune Tolerance in Healthy Pregnancies and Reproductive Diseases

Knockdown of vascular cell adhesion molecule 1 impedes transforming growth factor beta 1-mediated proliferation, migration, and invasion of endometriotic cyst stromal cells

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