Interleukin-33 modulates inflammation in endometriosis

Abstract

Endometriosis is a debilitating condition that is categorized by the abnormal growth of endometrial tissue outside the uterus. Although the pathogenesis of this disease remains unknown, it is well established that endometriosis patients exhibit immune dysfunction. Interleukin (IL)-33 is a danger signal that is a critical regulator of chronic inflammation. Although plasma and peritoneal fluid levels of IL-33 have been associated with deep infiltrating endometriosis, its contribution to the disease pathophysiology is unknown. We investigated the role of IL-33 in the pathology of endometriosis using patient samples, cell lines and a syngeneic mouse model. We found that endometriotic lesions produce significantly higher levels of IL-33 compared to the endometrium of healthy, fertile controls. In vitro stimulation of endometrial epithelial, endothelial and endometriotic epithelial cells with IL-33 led to the production of pro-inflammatory and angiogenic cytokines. In a syngeneic mouse model of endometriosis, IL-33 injections caused systemic inflammation, which manifested as an increase in plasma pro-inflammatory cytokines compared to control mice. Furthermore, endometriotic lesions from IL-33 treated mice were highly vascularized and exhibited increased proliferation. Collectively, we provide convincing evidence that IL-33 perpetuates inflammation, angiogenesis and lesion proliferation, which are critical events in the lesion survival and progression of endometriosis.

Chemosensitivity and chemoresistance in endometriosis – differences for ectopic versus eutopic cells

“…In ecESCs, the set of interest defined by the large-scale transcriptome analysis and qRT-PCR data included genes tightly connected with immune system functioning: the genes encoding interleukin 33 (IL33), cyclooxygenase 2 (PTGS2), and genes which expression is regulated by cytokines -pentraxin 3 (PTX3) and endothelial cell-specific molecule 1 (ESM1). The proteins encoded by all of the aforementioned genes have been reported to be connected with endometriosis (Cobellis et al, 2004;Fagotti et al, 2004;Kobayashi et al, 2012;Miller et al, 2017;Pelch et al, 2010), featuring correlation with endometriosis-associated inflammation and angiogenesis; inhibitors of PTGS2 have also been explored in the context of management of endometriosis-related pain (Cobellis et al, 2004).…”

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

“…Cells were incubated for 6 hours at 37 • C/5% CO 2 . Images were taken using a fluorescence microscope (EVOS FL, Thermo Scientific, Waltham, MA, USA), and tube formation was evaluated and quantified using NIH ImageJ software with the angiogenesis analyzer plug-in [38].…”

NLRC5 Inhibits Inflammation of Secretory Phase Ectopic Endometrial Stromal Cells by Up-Regulating Autophagy in Ovarian Endometriosis

“…Elevated serum IL-33 was associated with the intensity of painful preoperative symptoms and the extent and severity of the deeply infiltrating endometriosis (Santulli et al, 2012). Furthermore, IL-33 contributed to the lesion survival and progression of endometriosis by perpetuating inflammation, angiogenesis, and lesion proliferation (Miller et al, 2017). These findings demonstrate inflammation to be a common factor involved in the regulation of endometriosis.…”