Human chorionic gonadotropin regulates endothelial cell responsiveness to interleukin 1 and amplifies the cytokine-mediated effect on cell proliferation, migration and the release of angiogenic factors

Abstract

Problem: Successful embryonic implantation requires an appropriate communication network between the embryo and its near environment within the implantation site. Herein, we examined whether human chorionic gonadotropin (hCG), the major embryonic signal, targets endothelial cells and regulate their responsiveness to interleukin 1 (IL1), one of the earliest signals released by embryonic cells.

Method of study: Human microvascular endothelial cell proliferation and migration following exposure to various concentrations of hCG and/or IL1B for different time periods were analyzed by BrdU incorporation and wound healing assays. The expression of soluble (s) and membrane-bound (mb) IL1 receptors (IL1Rs), IL1R antagonist (IL1RN), luteinizing hormone/choriogonadotropin receptor (LHCGR), and IL8 was determined by real-time PCR, Western blot, and ELISA.

Results: Cell proliferation and migration increased in response to IL1B and further in the presence of hCG. IL1B up-regulated both the signaling IL1R1 and the inhibitory IL1R2, while adding hCG further increased IL1R1 and significantly downregulated IL1R2. This translated into an increased secretion of IL8, which was inhibited in cells where IL1R2 was overexpressed.

Conclusions: These findings reveal a new mechanism by which hCG may target endothelial cells to directly stimulate angiogenesis and favor embryonic growth.

Keywords: Angiogenesis; embryo implantation; endothelial cells; human chorionic gonadotropin; interleukin 1.