Abnormal peritoneal regulation of chemokine activation—The role of <scp>IL</scp>‐8 in pathogenesis of endometriosis

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

doi:10.1111/aji.12622

Cited by 92 publications

(68 citation statements)

References 71 publications

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“…2F). Although ROS levels were not measured in this particular arm of our study, this observation suggests a potential pathophysiological mechanism in endometriosis, and in general confirms the previous observation of elevated IL-8 levels in endometriosis 31 .…”

Section: The Lipid Peroxidation Product 4-hne Is Present In Ectopic Lsupporting

confidence: 91%

“…The angiogenic properties of this chemokine have long been recognized, particularly in oncology 45 , and also in endometriosis 46 . The clinical data from us and others that IL-8 is significantly elevated in the PF of women with endometriosis 31 and associated with pain 47 , further supports the observation that this cytokine promotes the disease in a dose-dependent manner 48,49 .…”

Section: Discussionsupporting

confidence: 66%

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Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

M-L.

Leo

Laux-Biehlmann

et al. 2020

Sci Rep

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Endometriosis is a common gynaecological disease of women in reproductive age, and is thought to arise from retrograde menstruation and implantation of endometrial tissue, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process thereby contributing to pain as cardinal symptom in endometriosis. Elevated reactive oxygen species (ROS) and oxidative stress have been postulated as factors in endometriosis pathogenesis. We here set out for a systematic study to identify novel mechanisms and pathways relating to oxidative stress in ectopic peritoneal lesions. Using combined proteomic and transcriptomic approaches, we identified novel targets including upregulated pro-oxidative enzymes, such as amine oxidase 3/vascular adhesion protein 1 (AOC3/VAP1) as well as downregulated protective factors, in particular alkenal reductase PTGR1 and methionine sulfoxide reductase. Consistent with an altered ROS landscape, we observed hemoglobin / iron overload, ROS production and lipid peroxidation in ectopic lesions. ROS-derived 4-hydroxy-2-nonenal induced interleukin IL-8 release from monocytes. Notably, AOC3 inhibitors provoked analgesic effects in inflammatory pain models in vivo, suggesting potential translational applicability.Endometriosis, affecting 5-10% of women in reproductive age, is a gynaecological disease characterized by the presence of ectopic endometrial tissue most often found in the pelvic cavity 1,2 . Retrograde menstruation is a widely accepted pathogenic mechanism for the formation of peritoneal lesions, in which uterine epithelial and stromal cells are disseminated during menstruation and implanted into the peritoneal cavity via the Fallopian tubes 3,4 . Peritoneal lesions are macroscopically classified based on colour, appearing as white, red, brown, or black lesions. This appearance seems to be determined by endometrial gland content and a variable adjacent stromal reaction, likely reflecting a chronicity process rather than different levels of disease activity 5 . Additional contributors to disease such as genetic, epigenetic and environmental factors exist, since a majority (90%) of women undergo retrograde menstruation associated with successful clearance of menstrual debris from the peritoneal cavity 3,6-9 . However, the formation of ectopic endometrial lesions is a signature event that leads to the hallmarks of disease, comprising sustained inflammation, severe and chronic pain, as well as subfertility 10,11 . www.nature.com/scientificreports www.nature.com/scientificreports/ proteomic and transcriptomic arms of the study distinct patient populations were used and further collection details are provided in the SI material.Protein extraction and sample preparation. Tissue material was homogenised and extracted, protein extracts were subjected to in-solution trypsin digestion and data processed as described 51 . Transcriptome analysis. Illumina compatible next-generation sequencing libraries were prepared and sequenced from ribosomal RNA depleted or...

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Section: The Lipid Peroxidation Product 4-hne Is Present In Ectopic Lsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 66%

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

M-L.

Leo

Laux-Biehlmann

et al. 2020

Sci Rep

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“…Angiogenesis plays an essential role in the growth and survival of endometriotic lesions . Previously, we and others demonstrated that ERK1/2 signaling contributes to growth of endometriotic lesions by enhancing proliferation of endometriotic stromal cells .…”

Section: Introductionmentioning

confidence: 80%

“…However, the most accepted etiological theory is retrograde menstruation, which enables recruitment of viable endometrial tissues into ectopic sites such as the peritoneal cavity with subsequent cellular attachment to peritoneal surfaces, implantation, and neovascularization prompting endometriotic tissue growth . Previous studies demonstrated elevated peritoneal levels of pro‐inflammatory chemokines monocyte chemo‐attractant protein (MCP)‐1, Interleukin (IL)‐8, fractalkine, and increased inflammatory cell recruitment, and/or elevated levels of IL‐6 and prostaglandins associated with pelvic pain in women with endometriosis …”

Section: Introductionmentioning

confidence: 99%

“…In view of our previous observations of the role played by ERK1/2 in human endometrial stromal cell proliferation, we hypothesized that endometriotic pro‐inflammatory milieu and/or local continuous E 2 production induce endothelial progenitor cell (angioblast) differentiation and survival by enhancing ERK1/2 activity, eliciting increased vascularization of ectopic endometrial implants. Thus, the current study compared ERK1/2 activity in endothelial cells in eutopic and ectopic endometrial sections and investigated both in vitro regulation and the role of ERK1/2 activity in HEEC differentiation, survival, angiogenesis, and expression of pro‐angiogenic cytokines MCP‐1, IL‐8, and vascular growth factor (VEGF) …”

Section: Introductionmentioning

confidence: 99%

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The extracellular signal‐regulated kinase 1/2 triggers angiogenesis in human ectopic endometrial implants by inducing angioblast differentiation and proliferation

Arlıer

Murk

Guzeloglu‐Kayisli

et al. 2017

American J Rep Immunol

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The role of inflammation, oxidative stress, angiogenesis, and apoptosis in the pathophysiology of endometriosis: Basic science and new insights based on gene expression

Samimi

Pourhanifeh

Mehdizadehkashi

et al. 2019

Journal Cellular Physiology

135

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Endometriosis is a frequent and chronic illness in young women which could be defined by the existence of endometrial stroma and glands outside of the normal site of the lining of the uterus. It has painful symptoms. The advanced stage of endometriosis may lead to gynecological malignancies, such as ovarian cancer, and other complications, including infertility. However, its exact physiopathology is not well known. Recent studies have shown the possible roles of inflammation along with oxidative stress. Additionally, angiogenesis and apoptosis dysregulation contribute to endometriosis pathophysiology. Therapeutic strategies and continuing attempts, to conquer endometriosis should be done regarding molecular signaling pathways. Thus, the present review summarizes current studies and focuses on molecular mechanisms.

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Abnormal peritoneal regulation of chemokine activation—The role of IL‐8 in pathogenesis of endometriosis

Abstract: It may act as an autocrine growth factor in the endometrium and promotes the vicious circle of endometrial cell attachment and, in consequence, may lead to a transformation from acute to chronic inflammation stage.

Cited by 92 publications

References 71 publications

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

The extracellular signal‐regulated kinase 1/2 triggers angiogenesis in human ectopic endometrial implants by inducing angioblast differentiation and proliferation

The role of inflammation, oxidative stress, angiogenesis, and apoptosis in the pathophysiology of endometriosis: Basic science and new insights based on gene expression

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