Induction of an angiogenic phenotype in endometriotic stromal cell cultures by interleukin-1β

• Published in: Molecular human reproduction Vol. 6; no. 3; pp. 269 - 275
• Main Authors: Lebovic, Dan I., Bentzien, Frauke, Chao, Victor A., Garrett, Evelyn N., Meng, Y.Gloria, Taylor, Robert N.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2000
• Subjects: angiogenesis factor; Biological and medical sciences; cytokines; endometriosis; Female genital diseases; Gynecology. Andrology. Obstetrics; interleukin-1; Medical sciences; neovascularization; Non tumoral diseases; Human; Endothelial cell; Angiogenic factor; Cytokine; Reverse transcription; Endometriosis; Interleukin 1β; Gene expression; In vitro; Female genital diseases; Polymerase chain reaction; Angiogenesis; Regulation(control); Interleukin 1; Uterine diseases; Female; Neovascularization; ELISA assay
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/6.3.269

Activated peritoneal macrophages are associated with endometriosis and may play a central role in its aetiology by releasing interleukin-1β (IL-1β) in response to refluxed endometrium. Pari passu with the establishment of endometriotic implants is the development of a vascular supply. In this study we investigated the angiogenic properties of two endometrial proteins, vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6), and assessed their production in response to IL-1β stimulation in human stromal cells isolated from normal endometrium (NE) and endometriotic lesions (EI). Proliferation of bovine brain capillary endothelial cells (BBCE) with a [3H]-thymidine incorporation assay was observed when VEGF (2.1 ± 0.2-fold; P < 0.05) or VEGF and IL-6 (1.8 ± 0.1-fold; P < 0.05) were added in vitro, relative to saline-treated control cultures. Northern blot analysis showed induction of VEGF mRNA (2.6-fold; P < 0.05) and IL-6 mRNA (6.3-fold; P < 0.05) transcripts in EI cells, but not NE cells, exposed to IL-1β. A similar induction was seen with VEGF and IL-6 protein secretion in the responsive EI cells. Reverse transcription–polymerase chain reaction (RT–PCR) for the IL-1 receptor type I (IL-1 RI) indicated that the differential effects of IL-1β on NE and EI cells was associated with 2.4 ± 0.1-fold more receptor mRNA in EI versus NE cells. We propose that the ability of IL-1β to activate an angiogenic phenotype in EI stromal cells but not in NE cells, is mediated by the IL-1 RI.