Profibrotic interleukin-33 is correlated with uterine leiomyoma tumour burden

Santulli, Piétro; Even, Marc; Chouzenoux, Sandrine; Millischer, Anne-Élodie; Borghese, Bruno; Ziegler, Dominique de; Batteux, Frédéric; Chapron, Charles

doi:10.1093/humrep/det238

Cited by 31 publications

(23 citation statements)

References 46 publications

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“…Chronic inflammation is associated with an overproduction of prostaglandins [17], metalloproteinases, cytokines and chemokines, creating a self-supporting loop that mantains and amplificates the progression of the disease [18–20]. Once the process is started, many profibrotic mediators also play a role in the fibrogenesis associated with endometriosis [21]. …”

Section: Introductionmentioning

confidence: 99%

Soluble Ligands for the NKG2D Receptor Are Released during Endometriosis and Correlate with Disease Severity

et al. 2015

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BackgroundEndometriosis is a benign gynaecological disease. Abundant bulk of evidence suggests that patients with endometriosis have an immunity dysfunction that enables ectopic endometrial cells to implant and proliferate. Previous studies show that natural killer cells have a pivotal role in the immune control of endometriosis.Methods and FindingsThis is a prospective laboratory study conducted in a tertiary-care university hospital between January 2011 and April 2013. We investigated non-pregnant, younger than 42-year-old patients (n= 202) during surgery for benign gynaecological conditions. After complete surgical exploration of the abdominopelvic cavity, 121 women with histologically proven endometriosis and 81 endometriosis-free controls women were enrolled. Patients with endometriosis were classified according to a surgical classification in three different types of endometriosis: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE). Peritoneal fluid samples were obtained from all study participants during the surgery in order to detect soluble NKG2D ligands (MICA, MICB and ULBP-2). When samples with undetectable peritoneal fluid levels of MICA, MICB and ULBP-2 were excluded, MICA ratio levels were significantly higher in endometriosis patients than in controls (median, 1.1 pg/mg; range, 0.1–143.5 versus median, 0.6 pg/mg; range, 0.1–3.5; p=0.003). In a similar manner peritoneal fluid MICB levels were also increased in endometriosis-affected patients compared with disease-free women (median, 4.6 pg/mg; range, 1.2–4702 versus median, 3.4 pg/mg; range, 0.7–20.1; p=0.001). According to the surgical classification, peritoneal fluid soluble MICA, MICB and ULBP-2 ratio levels were significantly increased in DIE as compared to controls (p=0.015, p=0.003 and p=0.045 respectively). MICA ratio levels also correlated with dysmenorrhea (r=0.232; p=0.029), total rAFS score (r=0.221; p=0.031) and adhesions rAFS score (r=0.221; p=0.031).ConclusionsWe demonstrate a significant increase of peritoneal fluid NKG2D ligands in women with endometriosis especially in those cases presenting DIE. This study suggests that NKG2D ligands shedding is a novel pathway in endometriosis complex pathogenesis that impairs NK cell function.

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Section: Introductionmentioning

confidence: 99%

Soluble Ligands for the NKG2D Receptor Are Released during Endometriosis and Correlate with Disease Severity

et al. 2015

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“…Among major cytokines, the expression of IL-1, IL-6, IL-11, IL-13, IL-15, IL-33, tumor necrosis factor (TNF) a, granulocyte-macrophage colony-stimulating factor have been implicated with their biological relevance to leiomyoma pathophysiology. 18,[40][41][42] Additionally, TGF-b has been shown to be overexpressed in leiomyomas versus myometrium and be both mitogenic and fibrogenic in these tissues. 43 Additional researches have demonstrated that TGF-b, IL-1 and TNF influence the secretion of enzymes (MMP2 and MMP9), 44 and IL-6 may induce hepatic C-reactive protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

Serum YKL-40 Level Positively Correlates With Uterine Leiomyomas

2016

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Uterine leiomyomas (ULMs) are the most common benign tumors in premenopausal women associated with major tissue fibrosis. It has been suggested that inflammatory response is associated with the development of ULM. YKL-40 is a chitinase-like protein present in serum of healthy participants, and its levels are increased in several human inflammatory diseases. However, the association between YKL-40 and ULM has not been reported. The aim of this study was to identify whether serum YKL-40 levels correlate with ULM. Premenopausal women with ULM (n = 61) and leiomyoma-free control women (n = 45) were recruited for this study. Serum YKL-40 levels were analyzed by enzyme-linked immunosorbent assay. Correlations were assessed by Spearman rank correlation test. Receiver-operating characteristics (ROC) curve was used to define the optimal cutoff value for predicting ULM. We found that serum YKL-40 levels in patients with ULM were significantly higher than in healthy controls (P < .001). Positive correlation was also observed between serum YKL-40 levels and leiomyoma weight (r = .92; P < .001). Moreover, ROC curves yielded robust area under the curve value (0.94) accompanied by high sensitivity (82.0%) and specificity (91.1%) in distinguishing patients with ULM from healthy controls. These findings suggest that elevated serum YKL-40 levels are associated with the existence of ULM, and YKL-40 might be a potential adjunct biomarker for diagnosis of ULM.

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“…The concept of inflammation actually fits into a theory of fibroid development based on an altered response to noxious stimuli; possibly tissue injury from extravasated menstrual blood into the myometrium, or hypoxia leading to altered tissue repair and fibrosis . Among major cytokines, the expression of IL‐1, IL‐6, IL‐11, IL‐13, IL‐15, IL‐33, tumor necrosis factor (TNF)‐α, granulocyte‐macrophage colony‐stimulating factor have been implicated with their biological relevance to leiomyoma pathophysiology . The expression profiles of many chemokines and chemokine receptors have also been characterized in leiomyomas and matched myometrium.…”

Section: Pathogenesis Of Uterine Fibroidsmentioning

confidence: 99%

“…been implicated with their biological relevance to leiomyoma pathophysiology [42][43][44][45][46][47]. The expression profiles of many chemokines and chemokine receptors have also been characterized in leiomyomas and matched myometrium.…”

Section: Resveratrolmentioning

confidence: 99%

Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: Promising options for prevention and treatment of uterine fibroids?

Islam

Akhtar

Ciavattini

et al. 2014

Molecular Nutrition Food Res

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Uterine leiomyomas (fibroids, myomas) are the most common benign tumors of female reproductive tract. They are highly prevalent, with 70–80% of women burdened by the end of their reproductive years. Fibroids are a leading cause of pelvic pain, abnormal vaginal bleeding, pressure on the bladder, miscarriage, and infertility. They are the leading indication for hysterectomy, and costs exceed 6 billion dollars annually in the United States. Unfortunately, no long-term medical treatments are available. Dysregulation of inflammatory processes are thought to be involved in the initiation of leiomyoma and extracellular matrix deposition, cell proliferation, and angiogenesis are the key cellular events implicated in leiomyoma growth. In modern pharmaceutical industries, dietary phytochemicals are used as source of new potential drugs for many kinds of tumors. Dietary phytochemicals may exert therapeutic effects by interfering with key cellular events of the tumorigenesis process. At present, a negligible number of phytochemicals have been tested as therapeutic agents against fibroids. In this context, our aim was to introduce some of the potential dietary phytochemicals that have shown anti-inflammatory, antiproliferative, antifibrotic, and antiangiogenic activities in different biological systems. This review could be useful to stimulate the evaluation of these phytochemicals as possible therapies for uterine fibroids.

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Profibrotic interleukin-33 is correlated with uterine leiomyoma tumour burden

Abstract: No funding, no conflict of interest.

Cited by 31 publications

References 46 publications

Soluble Ligands for the NKG2D Receptor Are Released during Endometriosis and Correlate with Disease Severity

Soluble Ligands for the NKG2D Receptor Are Released during Endometriosis and Correlate with Disease Severity

Serum YKL-40 Level Positively Correlates With Uterine Leiomyomas

Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: Promising options for prevention and treatment of uterine fibroids?

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