Influence of alpha-tumor necrosis factor and beta-interleukin-1 on production of angiogenetic factors and thymidine phosphorylase activity in immortalized human decidual fibroblasts in vitro.
OBJECTIVE
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-1beta) 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-1beta and TNF-alpha. TP activity was increased by TNF-alpha, but no increase was observed as a result of IL-1beta. 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-1beta and TNF-alpha stimulate decidual fibroblasts to up-regulate angiogenesis in the human decidua.
Hayashi
Takashi
T
Department of Obstetrics and Gynecology, Saitama Medical Centre, Saitama Medical School, Kawagoe, Saitama, Japan.
Matsuoka
Kikumi
K
Saitoh
Masahiro
M
Takeda
Satoru
S
Kimura
Masayuki
M
D042501:Angiogenic Proteins / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003656:Decidua / Q000166:cytology / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042501:Angiogenic Proteins; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013939:Thymidine Phosphorylase