Circulating and peritoneal fluid interleukin-6 levels and gene expression in pelvic endometriosis

Andrade, Vânia Teixeira De; Nácul, Andréa Prestes; Santos, Betânia Rodrigues dos; Lecke, Sheila Bünecker; Spritzer, Poli Mara; Morsch, Débora Martinho

doi:10.3892/etm.2017.4794

Cited by 20 publications

(12 citation statements)

References 36 publications

(48 reference statements)

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“…These high concentrations of TGF-β in the peritoneal fluid may create suitable conditions for the ectopic lesion formation. In a similar study of reference [ 39 ], the expression rate of IL-6 was also higher in patients with endometriosis and it had a dependence on the stage of the disease (higher in III/IV vs. I/II stage). Additionally, steroid hormone fluctuations occurring during the menstrual cycle seem not to affect the IL-6 synthesis.…”

Section: Resultssupporting

confidence: 56%

Inflammatory Mediators and Pain in Endometriosis: A Systematic Review

2021

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Background: pain is one of the main symptoms of endometriosis and it has a deleterious effect on a patients’ personal and social life. To date, the clinical management of pain includes prolonged medication use and, in some cases, surgery, both of which are disruptive events for patients. Hence, there is an urgency for the development of a sufficient non-invasive medical treatment. Inflammation is one of the causative factors of pain in endometriosis. It is well established that inflammatory mediators promote angiogenesis and interact with the sensory neurons inducing the pain signal; the threshold of pain varies and it depends on the state and location of the disease. The inhibition of inflammatory mediators’ synthesis might offer a novel and effective treatment of the pain that is caused by inflammation in endometriosis. Objectives: patients with endometriosis experience chronic pelvic pain, which is moderate to severe in terms of intensity. The objective of this systematic review is to highlight the inflammatory mediators that contribute to the induction of pain in endometriosis and present their biological mechanism of action. In addition, the authors aim to identify new targets for the development of novel treatments for chronic pelvic pain in patients with endometriosis. Data Sources: three databases (PubMed, Scopus, and Europe PMC) were searched in order to retrieve articles with the keywords ‘inflammation, pain, and endometriosis’ between the review period of 1 January 2016 to 31 December 2020. This review has been registered with PROSPERO (registry number: CRD42020171018). Eligibility Criteria: only original articles that presented the regulation of inflammatory mediators and related biological molecules in endometriosis and their contribution in the stimulation of pain signal were included. Data Extraction: two authors independently extracted data from articles, using predefined criteria. Results: the database search yielded 1871 articles, which were narrowed down to 56 relevant articles of interest according to the eligibility criteria. Conclusions: inflammatory factors that promote angiogenesis and neuroangiogenesis are promising targets for the treatment of inflammatory pain in endometriosis. Specifically, CXC chemokine family, chemokine fractalkine, and PGE2 have an active role in the induction of pain. Additionally, IL-1β appears to be the primary interleukin (IL), which stimulates the majority of the inflammatory factors that contribute to neuroangiogenesis along with IL-6. Finally, the role of Ninj1 and BDNF proteins needs further investigation.

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Section: Resultssupporting

confidence: 56%

Inflammatory Mediators and Pain in Endometriosis: A Systematic Review

2021

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“…in the peritoneal microenvironment and chronic inflammation have crucial roles in endometriosis development 6 as increased levels of pro-inflammatory cytokines and chemokines such as interleukin-6 (IL-6), IL-8, monocyte chemotactic protein-1 (MCP-1), and regulated upon activation, normal T cell expressed and secreted (RANTES) have been detected in peritoneal fluid (PF) of endometriotic patients compared to non-endometriotic participants, suggesting that these secretory products may be involved in endometriosis initiation and progression through the promotion of growth, adhesion, invasion and proliferation of endometrial cells. [7][8][9] Current treatment modalities for endometriosis are surgical and hormonal treatments, but the high incidence of disease recurrence and side effects of these therapies limit their usage in a long period. 10 Thus, in recent years, there has been an increasing emphasis on finding naturally occurring compounds for the management of endometriosis.…”

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confidence: 99%

Resveratrol treatment reduces expression of MCP‐1, IL‐6, IL‐8 and RANTES in endometriotic stromal cells

Kolahdouz‐Mohammadi

Shidfar

Khodaverdi

et al. 2020

J Cellular Molecular Medi

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Endometriosis is an enigmatic gynaecological disease characterized by ectopic implantation of endometrial like tissues in extra-uterine sites. 1 It afflicts approximately 10% of reproductive-aged women, 2%-11% of asymptomatic women, and almost half of the women experiencing chronic pelvic pain and associated with dysmenorrhoea, dyspareunia, pelvic pain and infertility. 1,2 The pathogenesis of endometriosis is not precisely understood. 3 Among numerous theories proposed to elucidate the pathophysiology of endometriosis, peritoneal implantation of viable endometrial cells during retrograde menstruation is the generally accepted one. 4 However, retrograde menstruation occurs in almost all reproductive-aged women, but only 10%-20% of them develop endometriosis, so other factors must be involved in implantation and survival of the displaced endometrial cells. 5 Based on recent findings, immune dysregulation

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“…Increased expression and function of NR4A2 have been reported to be related to a variety of signaling pathways, such as activation of the p53 pathway, which decreased NR4A2 expression; the p38 MAPK pathway, which could modulate the activity of Nurr1; and the Wnt signaling pathway inhibited by Nurr1 and PI3K-Akt-mTOR pathway (Beard et al, 2016). EM is a disease associated with chronic inflammation; the levels of inflammatory factors, such as IL-1, IL-6, IL-8, IL-10, and TNF-a, significantly increased in the follicular fluid of infertile patients with EM (Moberg et al, 2015;De Andrade et al, 2017). However, high levels of inflammatory cytokines, IL-1, IL-6, IL-8, and TNF-a, affect GCs and their function (Li et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Construction of Competing Endogenous RNA Networks Incorporating Transcription Factors to Reveal Differences in Granulosa Cells from Patients with Endometriosis

et al. 2021

Genetic Testing and Molecular Biomarkers

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This study was designed to reveal the molecular differences between granulosa cells (GCs) from patients with endometriosis and normal controls. Methods: RNA sequencing was performed on GCs from patients with EM-related infertility (n = 3) and controls (n = 3). Differentially expressed long noncoding RNAs [differentially expressed lncRNAs (DELs), jlog2 FCj>4, false discovery rate (FDR) <0.05] and genes [differentially expressed genes (DEGs), jlog2 FCj>1.4, FDR <0.05] in patients with EM-related infertility and controls were screened. Protein-protein interaction (PPI) networks of the DEGs were constructed. Then, mRNA-miRNA-lncRNA pairs based on DEGs and DELs were constructed by comprehensive bioinformatics analyses. In addition, overlapping genes identified from both the PPI and the mRNA-miRNA-lncRNA pairs were selected. Finally, a competing endogenous RNA (ceRNA) network incorporating transcription factors (TFs) was constructed. Results: A total of 25,806 lncRNAs and 19,684 mRNAs were detected, and 7 DELs and 46 DEGs were identified. Five hub genes from the PPI network were also identified. A single overlapping gene, NR4A2, from both the PPI network and mRNA-miRNA-lncRNA pairs was identified. Finally, a ceRNA network incorporating TFs, including one mRNA (NR4A2), one miRNA (hsa-miR-217), three lncRNAs (XIST, MCM3AP-AS1, and C17orf51), and five TFs (SRF, POLR2A, NRF1, MNT, and TCF7L2), was successfully constructed. Conclusions: The proposed ceRNA network and the prediction of TFs in GCs from EM-related infertility revealed differences in GCs from patients with EM. Importantly, the novel TFs, lncRNAs, miRNAs, and mRNAs involved in the ceRNA network might provide new insights into the underlying molecular mechanisms of EM-related infertility.

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Circulating and peritoneal fluid interleukin-6 levels and gene expression in pelvic endometriosis

Cited by 20 publications

References 36 publications

Inflammatory Mediators and Pain in Endometriosis: A Systematic Review

Inflammatory Mediators and Pain in Endometriosis: A Systematic Review

Resveratrol treatment reduces expression of MCP‐1, IL‐6, IL‐8 and RANTES in endometriotic stromal cells

Construction of Competing Endogenous RNA Networks Incorporating Transcription Factors to Reveal Differences in Granulosa Cells from Patients with Endometriosis

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