Interleukin-37b inhibits the growth of murine endometriosis-like lesions by regulating proliferation, invasion, angiogenesis and inflammation

He, Yongpei; Xiong, Ting; Guo, Fang; Du, Zhenhui; Fan, Yixian; Sun, Huanhuan; Zhao, Feng; Zhang, Guimei

doi:10.1093/molehr/gaaa014

Cited by 9 publications

(4 citation statements)

References 100 publications

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“…IL-37b also significantly inhibits MMP and VEGF-A mRNA and protein expression in an endometriosis murine model and in in vitro uterine segments (82). In addition, a mature form of IL-37b (IL-37bD1-45) effectively suppressed the migration and invasion of endometrial cancer cells by targeting the Rac1/NF-kB/MMP2 signal pathway (83).…”

Section: Suppression Of Cancer By Il-37 Il-37-induced Effects On Tumor Angiogenesis Migration and Progressionmentioning

confidence: 99%

Current Understanding of IL-37 in Human Health and Disease

Tao

2021

Front. Immunol.

116

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IL-37 is a recently discovered cytokine in the IL-1 family exerting broad protective effects on inflammatory diseases, autoimmune diseases, and cancer. Immune and non-immune cells produce the IL-37 precursor upon pro-inflammatory stimuli. Intracellularly, caspase-1 cleaves and activates IL-37, and its mature form binds to Smad3; this complex translocates into the nucleus where it suppresses cytokine production, consequently reducing inflammation. Extracellularly, IL-37 forms a complex with IL-18Rα and IL-1R8 (formerly TIR8 or SIGIRR) that transduces anti-inflammatory signals by the suppression of NF-κB and MAPK and the activation of Mer-PTEN-DOK pathways. During inflammation, IL-37 suppresses the expression of several pro-inflammatory cytokine in favor to the expression of the anti-inflammatory ones by the regulation of macrophage polarization, lipid metabolism, inflammasome function, TSLP synthesis and miRNAs function. Moreover, IL-37 not only regulates the innate and acquired immunity, but also improves aging-associated immunosenescence. Furthermore, IL-37 exerts an inhibitory effect on tumor angiogenesis and metastasis, and progression. Finally, IL-37 may have a potential ability to reduce excessive inflammation since it is aberrantly expressed in patients with inflammatory diseases, autoimmune diseases, and cancer, thus, it may be used as a marker for different types of diseases. Therefore, this review provides an updated view of the role of IL-37 in human health and disease, and discusses the potential of IL-37 as a therapeutic target and biomarker in inflammatory diseases, autoimmune diseases, and cancer.

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Section: Suppression Of Cancer By Il-37 Il-37-induced Effects On Tumor Angiogenesis Migration and Progressionmentioning

confidence: 99%

Current Understanding of IL-37 in Human Health and Disease

Tao

2021

Front. Immunol.

116

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“…Finally, while many studies point toward a broad inhibitory activity of IL-37 in innate inflammatory responses, effects of IL-37 on adaptive immunity, metabolism, angiogenesis, cell proliferation, and migration have also been reported (247)(248)(249)(250)(251)(252)(253)(254)(255).…”

Section: Il-37 Expression Activity and Signalingmentioning

confidence: 99%

IL-1 Family Antagonists in Mouse and Human Skin Inflammation

et al. 2021

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Interleukin (IL)-1 family cytokines initiate inflammatory responses, and shape innate and adaptive immunity. They play important roles in host defense, but excessive immune activation can also lead to the development of chronic inflammatory diseases. Dysregulated IL-1 family signaling is observed in a variety of skin disorders. In particular, IL-1 family cytokines have been linked to the pathogenesis of psoriasis and atopic dermatitis. The biological activity of pro-inflammatory IL-1 family agonists is controlled by the natural receptor antagonists IL-1Ra and IL-36Ra, as well as by the regulatory cytokines IL-37 and IL-38. These four anti-inflammatory IL-1 family members are constitutively and highly expressed at steady state in the epidermis, where keratinocytes are a major producing cell type. In this review, we provide an overview of the current knowledge concerning their regulatory roles in skin biology and inflammation and their therapeutic potential in human inflammatory skin diseases. We further highlight some common misunderstandings and less well-known observations, which persist in the field despite recent extensive interest for these cytokines.

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“…In the event of endometriosis, high proliferation of ectopic endometrial cells and endometrial metastasis, depending on invasive and migrating mechanisms, contribute substantially to the progression of endometriosis [ 6 ]. Therapeutic targets for inhibiting ectopic stromal cell (ESC) proliferation, migration, and invasion are considered to have potential for treating endometriosis [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor receptor 2 promotes the proliferation, migration, and invasion of ectopic stromal cells via activation of extracellular-signal-regulated kinase signaling pathway in endometriosis

Gao

Zhang

et al. 2022

Bioengineered

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Endometriosis is defined as the presence of endometrial tissues with cancer-like features in extrauterine locations. Fibroblast growth factor receptor 2 (FGFR2) is a tyrosine kinase that is involved in cancer pathogenesis. This study aimed to determine the role of FGFR2 in endometriosis. A total of 29 pairs of ectopic and eutopic endometrial tissues were collected from women with endometriosis. Endometrial tissues from women with hysteromyomas were considered as normal controls. Primary ectopic stromal cells (ESCs) were isolated from the ectopic endometrium. The role of FGFR2 in ESCs was assessed using immunohistochemistry, polymerase chain reaction, cell counting kit-8 assay, EdU staining, flow cytometry, transwell assay, and western blotting. The following signaling pathways were detected using bioinformatic analysis and confirmed in vitro . By searching the GSE171154, GSE86543, and GSE77182 datasets, FGFR2 was identified as an upregulated overlapping gene in endometriosis. Compared to eutopic and normal endometria, FGFR2 was highly expressed in ectopic tissues. Transfection of primary ESCs with FGFR2 small interfering RNA (siRNA) repressed the viability and proliferation of cells and induced apoptosis. FGFR2 siRNA inhibited the migration, invasion, and transforming growth factor-β1-triggered epithelial-mesenchymal transition (EMT). Extracellular signal-regulated kinase (ERK) signaling was found to be a downstream signaling pathway for FGFR2. The ERK1/2 inhibitor PD98059 was found to reverse the promoting effects of FGFR2 on ESC proliferation and invasion. FGFR2 silencing effectively inhibited the growth, migration, invasion, and EMT of ESCs. The effects of FGFR2 on endometriosis might be mediated via the activation of ERK signaling.

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Interleukin-37b inhibits the growth of murine endometriosis-like lesions by regulating proliferation, invasion, angiogenesis and inflammation

Cited by 9 publications

References 100 publications

Current Understanding of IL-37 in Human Health and Disease

Current Understanding of IL-37 in Human Health and Disease

IL-1 Family Antagonists in Mouse and Human Skin Inflammation

Fibroblast growth factor receptor 2 promotes the proliferation, migration, and invasion of ectopic stromal cells via activation of extracellular-signal-regulated kinase signaling pathway in endometriosis

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