17β-Estradiol and Lipopolysaccharide Additively Promote Pelvic Inflammation and Growth of Endometriosis

Abstract

Endometriosis is a multifactorial disease mostly affecting women of reproductive age. An additive effect between inflammation and stress reaction on the growth of endometriosis has been demonstrated. Here we investigated the combined effect between 17β-estradiol (E₂) and lipopolysaccharide (LPS) on pelvic inflammation and growth of endometriotic cells. Peritoneal fluid was collected from 46 women with endometriosis and 30 control women during laparoscopy. Peritoneal macrophages (Mφ) and stromal cells from eutopic/ectopic endometrial stromal cells (ESCs) were isolated from 10 women each with and without endometriosis in primary culture. Changes in cytokine secretion (interleukin 6 [IL-6] and tumor necrosis factor α [TNF-α]) by Mφ and proliferation of ESCs in response to single and combined treatment with E₂ and LPS were measured by enzyme-linked immunosorbent assay and by bromodeoxyuridine incorporation assay, respectively. A significantly increased secretion of IL-6 and TNF-α in Mφ culture media was found in response to E₂ (10⁻⁸ mol/L) compared to nontreated Mφ. This effect of E₂ was abrogated after pretreatment of cells with ICI 182720 (10⁻⁶ mol/L; an estrogen receptor [ER] antagonist). Combined treatment with E₂ and LPS (10 ng/mL) additively promoted IL-6 and TNF-α secretion by peritoneal Mφ and growth of eutopic/ectopic ESCs. The additive effects of E₂ + LPS on cytokine secretion and growth of ESCs were effectively suppressed after combined blocking of ER and Toll-like receptor 4. An additive effect was observed between E₂ and LPS on promoting proinflammatory response in pelvis and growth of endometriosis.

Keywords

endometriosis macrophages stromal cells estradiol LPS

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