Influence of α-tumor necrosis factor and β-interleukin-1 on production of angiogenetic factors and thymidine phosphorylase activity in immortalized human decidual fibroblasts in vitro

Aim: The aim of the present study was to investigate regulatory mechanisms of angiogenesis in the decidua using immortalized human decidual fibroblasts. Methods: A sample of decidual fibroblasts was taken from a woman in early pregnancy. A cell line, DE-1, was established by infecting the decidual fibroblasts with the simian virus 40 large T antigen. Using this cell line, the ability to produce vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), beta-transforming growth factor (TGF-beta), and thymidine phosphorylase (TP) activity was investigated using immunohistochemistry, and the influences of beta-interleukin-1 (IL-1 beta) and alpha-tumor necrosis factor (TNF-alpha) on these angiogenetic factors was investigated using enzyme-linked immunosorbent assays. Furthermore, the effects of TNF-alpha on proliferative capacity and apoptosis induction in DE-1 were studied. Results: It was demonstrated that DE-1 produced all of these angiogenetic factors. The production of VEGF, bFGF and TGF-beta respectively was enhanced by both IL-1 beta and TNF-alpha. TP activity was increased by TNF-alpha, but no increase was observed as a result of IL-1 beta. It was shown that TNF-alpha suppressed the proliferation of DE-1 cells and significantly increased the percentage of apoptotic cells. Conclusions: It is suggested that IL-1 beta and TNF-alpha stimulate decidual fibroblasts to up-regulate angiogenesis in the human decidua.