Upregulation of Interleukin 35 in Patients With Endometriosis Stimulates Cell Proliferation

Abstract

In this study, we investigated the expression of interleukin 35 (IL-35) and its receptors in endometriosis, analyzed the function of IL-35 in primary culture model of endometrial stromal cells (ESCs), and evaluated their clinicapathological significance. Peripheral blood (PB) and peritoneal fluid (PF) were collected from 37 women with endometriosis and 24 control women. The ectopic endometrium was obtained from patients with endometriosis undergoing laparoscopic surgery. The eutopic and normal endometrium were collected by endometrial biopsy. Levels of IL-35 in PB and PF were evaluated by enzyme-linked immunosorbent assay. Women with endometriosis had higher levels of IL-35 compared to controls both in PB and in PF. Levels of n IL-35 were increased in patients with advanced stage endometriosis compared to those with early stages in PF. A significant upregulation of IL-35 was observed in patients with ovarian endometriosis accompanied with pelvic implants (PI) compared to those without PI in PB and PF. The relative messenger RNA and protein expression of EBi3 and p35, the subunits of IL-35, were significantly higher in ectopic endometrium than in eutopic and healthy endometrium as measured by immunohistochemistry and quantitative polymerase chain reaction. The ESCs from endometriosis displayed a remarkable overexpression of IL-35 receptor subunits, IL12Rβ2 and gp130, compared to those from controls . Moreover, recombined human IL-35 protein stimulated the upregulation of IL12Rβ2 and gp130 and facilitated proliferation of ESCs. Our study provides the first evidence that IL-35 was involved in the pathogenesis of endometriosis through suppressing immunoreaction and promoting proliferation of ESCs. IL-35 may potentially serve as a biomarker for endometriosis.

Keywords

endometriosis interleukin 35 IL12Rβ2 gp130

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