IL-37 affects the occurrence and development of endometriosis by regulating the biological behavior of endometrial stromal cells through multiple signaling pathways
Abstract
Endometriosis (EMs) is a chronic inflammatory condition. Interleukin (IL)-37 is a member of the IL-1 family and an anti-inflammatory cytokine. This study aimed to evaluate the possible role of IL-37 in the EMs pathogenesis. We investigated the in vivo effect of IL-37 on EMs by injection with recombinant human IL-37 (rhIL-37) into EMs mice. Furthermore, we evaluated the in vitro effects of IL-37 on proliferation, adhesion, migration and invasiveness of endometrial stromal cells (ESCs), and explored whether Wnt/β-catenin and mitogen-activated protein kinase (MAPK) pathways were involved in this process. In cultured ESCs, IL-37 overexpression significantly suppressed both protein and mRNA expression of the inflammation-associated cytokines, including IL-1β, IL-6, IL-10 and tumor necrosis factor (TNF-α). Furthermore, IL-37 overexpression significantly inhibited ESCs proliferation, adhesion, migration, invasion and the activity of matrix metalloproteinase (MMP)-2 and MMP-9. In contrast, knockdown of IL-37 exerted the opposite effects. Importantly, the IL-37-mediated action in ESCs was through inactivation of Wnt/β-catenin, p38 MAPK, extracellular signal-related kinases MAPK and c-Jun N-terminal kinase MAPK pathways. Moreover, EMs mice treated with rhIL-37 showed the decreased endometriotic-like lesion size and lesion weight, lower expression of IL-1β, IL-6, IL-10, TNF-α, vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-I (ICAM-I) and MMP-2/9 activity in peritoneal fluid compared with the wide type (WT) EMs mice. These findings suggest that IL-37 suppresses cell proliferation, adhesion, migration and invasion of human ESCs through multiple signaling pathways, thereby affecting the occurrence and development of EMs.
Acknowledgments
The present study was supported by the New Xiangya Talent Project of The Third Xiangya Hospital of Central South University (Grant No. JY201706).
Conflict of interest statement: The authors declare no conflicts of interest.
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©2018 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
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- Five decades of research on mitochondrial NADH-quinone oxidoreductase (complex I)
- Modifications in small nuclear RNAs and their roles in spliceosome assembly and function
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- MAC30 knockdown involved in the activation of the Hippo signaling pathway in breast cancer cells
- Inhibition of JAK2/STAT3 signaling suppresses bone marrow stromal cells proliferation and osteogenic differentiation, and impairs bone defect healing
- IL-37 affects the occurrence and development of endometriosis by regulating the biological behavior of endometrial stromal cells through multiple signaling pathways
- Resveratrol alleviates early brain injury following subarachnoid hemorrhage: possible involvement of the AMPK/SIRT1/autophagy signaling pathway
Articles in the same Issue
- Frontmatter
- Reviews
- Interaction of volatile organic compounds and underlying liver disease: a new paradigm for risk
- Five decades of research on mitochondrial NADH-quinone oxidoreductase (complex I)
- Modifications in small nuclear RNAs and their roles in spliceosome assembly and function
- Minireview
- Transcriptional regulation of human defense peptides: a new direction in infection control
- Research Articles/Short Communications
- Cell Biology and Signaling
- Down-regulated paxillin suppresses cell proliferation and invasion by inhibiting M2 macrophage polarization in colon cancer
- p21Waf1 deficiency does not decrease DNA repair in E1A+cHa-Ras transformed cells by HDI sodium butyrate
- MAC30 knockdown involved in the activation of the Hippo signaling pathway in breast cancer cells
- Inhibition of JAK2/STAT3 signaling suppresses bone marrow stromal cells proliferation and osteogenic differentiation, and impairs bone defect healing
- IL-37 affects the occurrence and development of endometriosis by regulating the biological behavior of endometrial stromal cells through multiple signaling pathways
- Resveratrol alleviates early brain injury following subarachnoid hemorrhage: possible involvement of the AMPK/SIRT1/autophagy signaling pathway