Possible involvement of crosstalk between endometrial cells and mast cells in the development of endometriosis via CCL8/CCR1

• Published in: Biomedicine & pharmacotherapy Vol. 129; p. 110476
• Main Authors: Li, Tiantian, Wang, Jianzhang, Guo, Xinyue, Yu, Qin, Ding, Shaojie, Xu, Xinxin, Peng, Yangying, Zhu, Libo, Zou, Gen, Zhang, Xinmei
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.09.2020; Elsevier
• Subjects: Angiogenesis; Animals; Case-Control Studies; CCL8; CCR1; Cell Communication - drug effects; Cells, Cultured; Chemokine CCL8 - genetics; Chemokine CCL8 - metabolism; Coculture Techniques; Disease Models, Animal; Endometriosis; Endometriosis - metabolism; Endometriosis - pathology; Endometriosis - prevention & control; Endometrium - blood supply; Endometrium - drug effects; Endometrium - metabolism; Endometrium - pathology; Endothelial Cells - metabolism; Endothelial Cells - pathology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Humans; Mast cell; Mast Cells - metabolism; Mast Cells - pathology; Mice, Inbred BALB C; Migration; Neovascularization, Pathologic; Phenylurea Compounds - pharmacology; Piperidines - pharmacology; Receptors, CCR1 - antagonists & inhibitors; Receptors, CCR1 - genetics; Receptors, CCR1 - metabolism; Signal Transduction; Stromal Cells - metabolism; Stromal Cells - pathology; CCR1; Angiogenesis; Endometriosis; Mast cell; CCL8; Migration
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.110476

This study demonstrates that the crosstalk between endometrial cells and mast cells promotes the migratory ability of endometrial epithelial and stromal cells and angiogenesis via CCL8/CCR1, thereby contributing to the development of endometriosis. [Display omitted] •Endometrial cells promote the secretion of CCL8 from mast cells by their crosstalk.•CCL8 promotes the migratory ability of endometrial cells and novel angiogenesis.•CCL8 takes its effects via CCL8/CCR1.•CCR1 antagonist suppresses the development of endometriosis. The density and the activity of mast cells are associated with endometriosis. However, the role of mast cells on the pathogenesis of endometriosis remains unclear. Our study aims to investigate whether endometrial cells interact with mast cells and the involvement of their crosstalk in the development of endometriosis. The transwell assay was applied to investigate the effect of mast cells on the migratory ability of human primary endometrial cells. Mast cells were cocultured with endometrial epithelial and stromal cells respectively and total RNAs were isolated and subjected to mRNA sequencing. Next, the transwell assay, CCK-8, and tube formation were applied to study the role of CCL8 on the endometrial and endothelial cells in vitro. The mouse model was also established to confirm the role of CCL8 in the development and angiogenesis of endometriosis. CCL8 was up-regulated in mast cells when cocultured with endometrial cells. CCL8 was highly expressed in the ectopic endometrium and the serum of patients with endometriosis. CCL8 promoted the migratory ability of endometrial epithelial and stromal cells and increased the proliferation, migration, and tube formation of endothelial cells. CCR1, the receptor of CCL8, was over-expressed in the ectopic endometrium and colocalized with blood vessels in ovarian endometriomas. The inhibition of CCR1 suppressed the development and angiogenesis of endometriosis in vivo. The crosstalk between endometrial cells and mast cells in the development of endometriosis via CCL8/CCR1 was demonstrated, thereby providing a new treatment strategy for endometriosis.