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The CCL 17‐ CCR 4 axis between endometrial stromal cells and macrophages contributes to the high levels of IL ‐6 in ectopic milieu
Author(s) -
Zhou WenJie,
Hou XinXin,
Wang XiaoQiu,
Li DaJin
Publication year - 2017
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12644
Subject(s) - stromal cell , endometriosis , flow cytometry , proinflammatory cytokine , chemokine , endometrium , andrology , chemistry , peritoneal fluid , endocrinology , medicine , inflammation , immunology
Endometriosis is a chronic inflammatory disease characterized by the elevation of proinflammatory cytokines, such as IL ‐6, in the peritoneal fluid. However, the precise mechanism of the highly elevated IL ‐6 levels in ectopic milieu remains unclear. The aim of this study was to investigate whether the cross talk between endometrial stromal cells ( ESC s) and macrophages contributes to the elevated IL ‐6 production. Samples of endometrium and ectopic tissues were obtained from patients with or without endometriosis. The peripheral blood samples were collected from healthy volunteers. Enzyme‐linked immunosorbent assay ( ELISA ) was for IL ‐6 levels in peritoneal fluid and cell culture supernatant. In‐Cell Western assay was used for protein expression of CCL 17 and phosphorylation levels of ERK , JNK , and P38. Immunohistochemistry was performed on normal, eutopic endometrium and ectopic tissues to analyze CCL 17 expression. Flow cytometry was applied to detect the expression of CCR 4, IL ‐6, and the phosphorylation levels of NF ‐κB. Patients with endometriosis have higher levels of IL ‐6 in peritoneal fluid compared to the control. The co‐culture of ESC s and macrophages produce more IL ‐6 than cultured alone, respectively. The eutopic endometrium had significantly higher expression of CCL 17 compared to normal endometrium, and the ectopic tissues had the highest expression. IL ‐6 induced CCL 17 secretion in ESC s via activating JNK signaling pathway, CCL 17 upregulated the expression of its receptor CCR 4 on macrophages. Furthermore, CCL 17‐ CCR 4 axis subsequently led to excessive IL ‐6 production in macrophages by activating NF ‐κB. These findings suggest that the cross talk between ESC s and macrophages promotes the expression of CCL 17 in ESC s and CCR 4 on macrophages, which contributes to the high levels of IL ‐6 in ectopic milieu.