Interleukin-1 beta stimulates colony-stimulating factor-1 production in placental villous core mesenchymal cells

Abstract

The human placenta is known to produce hematopoietic growth factors, including colony-stimulating factor-1 (CSF-1). We have previously demonstrated interleukin-1 beta (IL-1 beta) production by decidualized endometrium during pregnancy. Since IL-1 stimulates CSF-1 production in fibroblasts, endothelial cells, and bone marrow stromal cells, our present study was designed to determine whether IL-1 could also regulate CSF-1 production by placental villous core mesenchymal cells. Initial studies using enzymatic digestion separation of the trophoblast and villous core demonstrated that CSF-1 mRNA is mainly expressed in the placental villous core. Subsequently, long term monolayer cultures of villous core mesenchymal cells isolated from 9- to 16-week gestation placentas were established after enzymatic dissociation of intact placental villi to study the regulation of villous core cell CSF-1 production. The morphology of the cells and immunohistochemical staining for vimentin, cytokeratin, and CD45 antigen confirmed that cultured cells were more than 95% mesenchymal fibroblasts. Time-course experiments demonstrated a maximal increase in CSF-1 mRNA expression of approximately 6.0-fold over baseline levels 3 h after IL-1 beta treatment (10 ng/mL), whereas increased CSF-1 protein production was first detected in the culture medium 3 h after IL-1 beta treatment and rose progressively over 42 hours. Villous core mesenchymal cells incubated with 0-10 ng/mL IL-1 beta demonstrated a specific dose-response relationship for CSF-1 mRNA expression and protein production, first seen at 0.10 ng/mL and maximal with 10 ng/mL IL-1 beta. These results demonstrate that production of CSF-1 by placental villous core mesenchymal cells can be stimulated by IL-1 beta in vitro and suggest that decidual IL-1 may regulate placental CSF-1 production in vivo.