Induction of an angiogenic phenotype in endometriotic stromal cell cultures by interleukin-1beta.
Activated peritoneal macrophages are associated with endometriosis and may play a central role in its aetiology by releasing interleukin-1beta (IL-1beta) 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-1beta stimulation in human stromal cells isolated from normal endometrium (NE) and endometriotic lesions (EI). Proliferation of bovine brain capillary endothelial cells (BBCE) with a [(3)H]-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-1beta. 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-1beta 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-1beta to activate an angiogenic phenotype in EI stromal cells but not in NE cells, is mediated by the IL-1 RI.
Lebovic
D I
DI
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94143-0556, USA.
Bentzien
F
F
Chao
V A
VA
Garrett
E N
EN
Meng
Y G
YG
Taylor
R N
RN
D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004715:Endometriosis / Q000473:pathology; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D010641:Phenotype; D017472:Receptors, Interleukin-1 / Q000235:genetics; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D016228:Endothelial Growth Factors; D007375:Interleukin-1; D015850:Interleukin-6; D008222:Lymphokines; D017472:Receptors, Interleukin-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors