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Schematic presentation of cell population and the origin of anti-inflammatory cytokines in endometriotic milieu. PF peritoneal fluid
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Although the pathogenesis of endometriosis is not fully understood, it is often considered to be an inflammatory disease. An increasing number of studies suggest that differential expression of anti-inflammatory cytokines (e.g., interleukin-4 and -10, and transforming growth factor-β1) occurs in women with endometriosis, including in serum, periton...
Context in source publication
Context 1
... with a crucial role in the mainte- nance of self-tolerance and immune homeostasis, and are involved in various human diseases, such as autoimmune diseases and cancer [108][109][110]. As the two key functional cytokines, IL-10 and TGF-β are secreted by Tregs in ectopic lesions and PF, and are significantly increased in patients with endometriosis (Fig. 2) [54,74,77,[111][112][113]. As opposed to pro-inflammatory interferon (IFN)-γ + Th17 cells, IL-10 production by Th17 cells is critical for limiting auto- immunity and inflammatory responses. This unique subset of Th17 cells simultaneously secretes IL-10 and IL-17A in the PF of women with endometriosis [48]. Macrophages are the most ...
Citations
... In addition, when the inflammatory activity in the peritoneal fluid decreases, the level of the anti-inflammatory factor IL-37 increases. When inflammatory substances cannot be removed, an inflammatory response may occur, which spreads throughout the body, with long-term effects on the immune system (Symons et al., 2018;Zhou et al., 2019). ...
In recent years, a growing body of research has confirmed that the gut microbiota plays a major role in the maintenance of human health and disease. A gut microbiota imbalance can lead to the development of many diseases, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome, endometriosis, and cancer. Short-chain fatty acids are metabolites of specific intestinal bacteria and are crucial for maintaining intestinal homeostasis and regulating metabolism and immunity. Endometriosis is the result of cell proliferation, escape from immune surveillance, and invasive metastasis. There is a strong correlation between the anti-proliferative and anti-inflammatory effects of short-chain fatty acids produced by gut microbes and the development of endometriosis. Given that the mechanism of action of gut microbiota and Short-chain fatty acids in endometriosis remain unclear, this paper aims to provide a comprehensive review of the complex interactions between intestinal flora, short-chain fatty acids and endometriosis. In addition, we explored potential microbial-based treatment strategies for endometriosis, providing new insights into the future development of diagnostic tests and prevention and treatment methods for endometriosis.
... Therefore, PRP's anti-inflammatory properties are essential for lowering inflammation in endometrial tissue, which lowers fibrosis and fosters regeneration. PRP treatment addresses inflammation-related issues and supports the recovery effects inside the endometrium by way of controlling the inflammatory response, providing a feasible strategy for encouraging tissue repair and regeneration [50]. ...
... On one hand, endometriosis-related inflammation is associated with higher levels of cytokines and, on the other hand, in control patients (i.e. without inflammatory disease) cytokine levels are lower [15,16]. Based on these hypotheses, we planned to study inflammation at the molecular level by establishing the cytokine profile in patients with Essure® implants compared to two other groups: patients with endometriosis and a control group. ...
... Cytokines are directly involved in the systemic inflammatory response syndrome. Pro and anti-inflammatory cytokines interact in a complex manner and are known to play a crucial role in the pathogenesis of endometriosis [15,16]. ...
... network of cytokines. These cytokines have been considered by certain authors as possible non-invasive plasma biomarkers for diagnosis and/ or potential target for medical treatment [15,16,20]. We did not find any specific cytokines in the peritoneal fluid from patients with Essure® microcoil. ...
... M1 mainly mediates tissue damage and inflammation, while M2 is mainly involved in tissue repair and anti-inflammatory processes (53,54). Growing evidence suggests that the abdominal microenvironment in EMs patients contributes to macrophages M2 polarization to facilitate progression of EMs (56,57). Sun et al. demonstrated that EMs-EVs can remodel the macrophage phenotype to M2 polarization and attenuate the phagocytic ability of macrophages both in vivo and in vitro (41). ...
Endometriosis is a chronic inflammatory gynecological disease, which profoundly jeopardizes women’s quality of life and places a significant medical burden on society. The pathogenesis of endometriosis remains unclear, posing major clinical challenges in diagnosis and treatment. There is an urgent demand for the development of innovative non-invasive diagnostic techniques and the identification of therapeutic targets. Extracellular vesicles, recognized for transporting a diverse array of signaling molecules, have garnered extensive attention as a novel mode of intercellular communication. A burgeoning body of research indicates that extracellular vesicles play a pivotal role in the pathogenesis of endometriosis, which may provide possibility and prospect for both diagnosis and treatment. In light of this context, this article focuses on the involvement of extracellular vesicles in the pathogenesis of endometriosis, which deliver information among endometrial stromal cells, macrophages, mesenchymal stem cells, and other cells, and explores their potential applications in the diagnosis and treatment, conducing to the emergence of new strategies for clinical diagnosis and treatment.
... An increasing number of studies have shown that both EM and IBD involve activation of immune and inflammatory pathways (32,33). During the progression of EM, specific anti-inflammatory cytokines (IL-1 beta, IL-5, IL-6, IL-7, IL-12, IL-4, and IL-10) and immune cells (M2 macrophage, neutrophil, M1 macrophage, and activated mast cells) are critical in supporting the persistence, expansion, infiltration, differentiation, angiogenesis, and immune evasion of endometriotic lesions in a multitude of pathogenic ways (34)(35)(36)(37). The pathogenesis of IBD is closely linked to dysregulation of the immune system. ...
Introduction
Over the past decades, immune dysregulation has been consistently demonstrated being common charactoristics of endometriosis (EM) and Inflammatory Bowel Disease (IBD) in numerous studies. However, the underlying pathological mechanisms remain unknown. In this study, bioinformatics techniques were used to screen large-scale gene expression data for plausible correlations at the molecular level in order to identify common pathogenic pathways between EM and IBD.
Methods
Based on the EM transcriptomic datasets GSE7305 and GSE23339, as well as the IBD transcriptomic datasets GSE87466 and GSE126124, differential gene analysis was performed using the limma package in the R environment. Co-expressed differentially expressed genes were identified, and a protein-protein interaction (PPI) network for the differentially expressed genes was constructed using the 11.5 version of the STRING database. The MCODE tool in Cytoscape facilitated filtering out protein interaction subnetworks. Key genes in the PPI network were identified through two topological analysis algorithms (MCC and Degree) from the CytoHubba plugin. Upset was used for visualization of these key genes. The diagnostic value of gene expression levels for these key genes was assessed using the Receiver Operating Characteristic (ROC) curve and Area Under the Curve (AUC) The CIBERSORT algorithm determined the infiltration status of 22 immune cell subtypes, exploring differences between EM and IBD patients in both control and disease groups. Finally, different gene expression trends shared by EM and IBD were input into CMap to identify small molecule compounds with potential therapeutic effects.
Results
113 differentially expressed genes (DEGs) that were co-expressed in EM and IBD have been identified, comprising 28 down-regulated genes and 86 up-regulated genes. The co-expression differential gene of EM and IBD in the functional enrichment analyses focused on immune response activation, circulating immunoglobulin-mediated humoral immune response and humoral immune response. Five hub genes (SERPING1、VCAM1、CLU、C3、CD55) were identified through the Protein-protein Interaction network and MCODE.High Area Under the Curve (AUC) values of Receiver Operating Characteristic (ROC) curves for 5hub genes indicate the predictive ability for disease occurrence.These hub genes could be used as potential biomarkers for the development of EM and IBD. Furthermore, the CMap database identified a total of 9 small molecule compounds (TTNPB、CAY-10577、PD-0325901 etc.) targeting therapeutic genes for EM and IBD.
Discussion
Our research revealed common pathogenic mechanisms between EM and IBD, particularly emphasizing immune regulation and cell signalling, indicating the significance of immune factors in the occurence and progression of both diseases. By elucidating shared mechanisms, our study provides novel avenues for the prevention and treatment of EM and IBD.
... On one hand, endometriosis-related inflammation is associated with higher levels of cytokines and, on the other hand, in control patients (i.e. without inflammatory disease) cytokine levels are lower [15,16]. Based on these hypotheses, we planned to study inflammation at the molecular level by establishing the cytokine profile in patients with Essure® implants compared to two other groups: patients with endometriosis and a control group. ...
... Cytokines are directly involved in the systemic inflammatory response syndrome. Pro and anti-inflammatory cytokines interact in a complex manner and are known to play a crucial role in the pathogenesis of endometriosis [15,16]. ...
... network of cytokines. These cytokines have been considered by certain authors as possible non-invasive plasma biomarkers for diagnosis and/ or potential target for medical treatment [15,16,20]. We did not find any specific cytokines in the peritoneal fluid from patients with Essure® microcoil. ...
... We strongly believe that pain persistency after surgical treatment could be related to the intrinsic nature of endometriosis as a chronic inflammatory disease leading to an up-regulation of pain sensitization promoting cytokines, nociceptive, and neuropathic pathways activation [53,54]. On the contrary, some authors suggested that endometriosis progression, growth, and invasion are related to an indispensable role of anti-inflammatory cytokines [55]. This reflects the poor comprehension of the real endometriosis etiology and pathogenesis and how a targeted medical or surgical treatment remains today not applicable. ...
Background: The validation of laser usage during laparoscopic procedures, notably by Camran Nezhat in the late 1980s, has been significant. Lasers offer precision and depth control in tissue vaporization without bleeding. Surgical intervention remains central in managing endometriosis-associated pain and infertility, especially for patients unresponsive to hormonal therapy. Methods: This retrospective cohort study included 200 patients with superficial peritoneal endometriosis (SPE) who underwent laparoscopic laser vaporization. Surgery was performed using a CO2 laser, and histological confirmation of endometriosis was obtained for all cases. Pain scores and SF-36 questionnaire domains were assessed preoperatively and postoperatively. Fertility outcomes were evaluated among patients desiring pregnancy. Results: Significant improvements in pain score and SF-36 questionnaire domains were observed postoperatively (p-value < 0.01), indicating enhanced quality of life. Among infertile patients with an active desire for pregnancy, surgical treatment showed an overall pregnancy rate after surgery of 93.7% (p-value < 0.01), including 75.7% natural pregnancies and 24.3% IVF. Laser vaporization enabled precise lesion removal with minimal tissue damage, short operative time, and minimal blood loss. Conclusions: Laparoscopic laser vaporization is an effective treatment for SPE, offering pain relief, improved quality of life, and favorable fertility outcomes. Further research is needed to validate these results in terms of pain control and fertility.
... As a result, the high level of PGE2 produced by COX-2 + NK cells may induce the differentiation of Treg cells, promote their function, and further increase the survival, migration, and invasion of endometriotic cells [71]. Additionally, the anti-inflammatory cytokines IL-10 and TGF-β can suppress the proliferation of CD4 + CD25 − T cells [72], inducing immunotolerance and contributing to the evasion of ectopic endometrial cells. We have also found that PPD, as a competitive antagonist of estrogen, can downregulate the expression of IL-10 and upregulate the expression of IFN-γ in NK cells, indicating the regulatory effect of estrogen on IL-10 and IFN-γ expression in NK cells [58]. ...
Endometriosis is a common estrogen-dependent condition that impacts 8–10% of women in their reproductive age, resulting in notable pain, morbidity, and infertility. Despite extensive research endeavors, the precise cause of endometriosis remains elusive, and the mechanisms contributing to its associated infertility are still not well comprehended. Natural killer (NK) cells, vital innate immune cells crucial for successful pregnancy, have been investigated for their potential involvement in the pathogenesis of endometriosis. Prior research has mainly concentrated on the diminished cytotoxicity of NK cells in endometrial fragments that evade the uterus. Interestingly, accumulating evidence suggests that NK cells play multifaceted roles in regulating the biology of endometrial stromal cells (ESCs), promoting local immune tolerance, influencing endometrial receptivity, oocyte development, and embryo implantation, thereby contributing to infertility and miscarriage in patients with endometriosis. In this comprehensive review, our goal is to summarize the current literature and provide an overview of the implications of NK cells in endometriosis, especially concerning infertility and pregnancy loss, under the influence of estrogen.
... The immune system plays a key role in endometrios-associated pain, infertility, and adverse pregnancy outcomes. Inflammatory cytokines are involved in survival, growth, invasion, differentiation, angiogenesis, and immune escape of endometriosis lesions (Zhou et al. 2019). Immune cells in the endometrium, including T lymphocytes, macrophages and natural killer cells play an important role in maintaining immune tolerance (Vallvé-Juanico et al. 2019). ...
Epigenetic regulation plays an essential role in immunity and inflammation in endometriosis. In this study, we aimed to explore differences in m6A regulators between endometriosis patients and normal women and analyze the effect of m6A modification on immune and inflammatory microenvironment. The samples for analysis were downloaded from the Gene Expression Omnibus database, including ectopic endometrium (EC), eutopic endometrium (EU), and normal eutopic endometrium (NM) samples from non-endometriosis women. The validation process involved utilizing our previous RNA-sequencing data. Subsequently, a correlation analysis was performed to ascertain the relationship between m6A and the inflammatory microenvironment profile, encompassing infiltrating immunocytes, immune-inflammation reaction gene sets, and human leukocyte antigen genes. LASSO analyses were used to develop risk signature. The findings of this study indicate that the m6A regulators FTO were observed to be significantly up-regulated, while YTHDF2, CBLL1, and METTL3 were down-regulated in endometriosis tissues. The CIBERSORT analysis revealed that the local inflammatory microenvironment of ectopic lesions plays a crucial role in the development of endometriosis. Notably, M2 macrophages exhibited a significant difference between the EC and NM groups. Moreover, M2 macrophages demonstrated a positive correlation with FTO (0.39) and a negative correlation with CBLL1 (− 0.35). Furthermore, consistent clustering of EC and EU samples resulted in the identification of three distinct cell subtypes. Among different cell subtypes, significant differences were in immunoinfiltrating cells, plasma cells, naive CD4 T cells, memory activated CD4 T cells, gamma delta T cells, resting NK cells and activated NK cells but not in macrophages. Furthermore, the identification of various compounds capable of targeting these m6A genes was achieved. In conclusions, our integrated bioinformatics analysis results demonstrated that m6A-related genes METTL3, CBLL1 and YTHDF2 may be useful biomarkers for endometriosis in ectopic endometrium. The potential therapeutic approach of targeting m6A regulators holds promise for the treatment of endometriosis.
... We strongly believe that pain persistency after surgical treatment could be related to the intrinsic nature of endometriosis as a chronic inflammatory disease leading to an up-regulation of pain sensitization promoting cytokines, nociceptive and neuropathic pathways activation [49,50]. On the contrary, some authors suggested that endometriosis progression, growth, and invasion are related to an indispensable role of anti-inflammatory cytokines [51]. This reflects the poor comprehension of the real endometriosis etiology and pathogenesis and how a targeted medical or surgical treatment remains today not applicable. ...
Background: The validation of laser usage during laparoscopic procedures, notably by Camran Nezhat in the late 1980s, has been significant. Lasers offer precision and depth control in tissue vaporization without bleeding. Surgical intervention remains central in managing endometrio-sis-associated pain and infertility, especially for patients unresponsive to hormonal therapy. Methods: This retrospective cohort study included 200 patients with SPE who underwent laparo-scopic laser vaporization. Surgery was performed using a CO2 laser, and histological confirma-tion of endometriosis was obtained for all cases. Pain scores and SF-36 questionnaire domains were assessed preoperatively and postoperatively. Fertility outcomes were evaluated among pa-tients desiring pregnancy. Results: Significant improvements in pain score and SF-36 questionnaire domains were ob-served postoperatively (p-value
