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Mol. Hum. Reprod. Advance Access published online on April 8, 2004

Molecular Human Reproduction, doi:10.1093/molehr/gah060
© 2004 by Oxford University Press
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Received December 22, 2003
Revised March 12, 2004
Accepted March 19, 2004

Article

Regulation of Fas ligand expression by vascular endothelial growth factor in endometrial stromal cells in vitro

M. Berkkanoglu 1, O. Guzeloglu-Kayisli 2, U.A. Kayisli 3, B.F. Selam 1, A. Arici 1*

1 Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520, USA
2 Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Medical Biology and Genetics, Akdeniz University School of Medicine, Antalya, Turkey, 07070
3 Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Histology and Embryology, Akdeniz University School of Medicine, Antalya, Turkey, 07070

* To whom correspondence should be addressed. E-mail: aydin.arici{at}yale.edu.


   Abstract

When Fas ligand (FasL) interacts with the Fas receptor, it induces apoptosis through autocrine and/or paracrine signalling. Vascular endothelial growth factor (VEGF) is a potent mitogenic cytokine. VEGF plays a role during remodelling of the endometrium following menstruation. We hypothesized that, by regulating FasL expression, VEGF may play a role in endometrial stromal cell survival by decreasing autocrine apoptotic signalling. We aimed to determine the expression of FasL in cultured endometrial stromal cells and its modulation by VEGF. VEGF induced a decrease in both FasL-positive cell number and FasL intensity as determined by immunocytochemistry and western blot respectively (P < 0.05). These effects of VEGF were observed in a concentration-dependent manner (10-42%; P < 0.05). Anti-VEGF neutralizing antibody alone resulted in an increase in the FasL expression. When combined with VEGF, anti-VEGF reversed the VEGF-induced decrease in FasL level up to 100% (P < 0.05). In addition, western blot analysis showed that FasL expression in endometrial stromal cells demonstrated a cyclic change every 12 h during 48 h of incubation. These results suggest that down-regulation of FasL by VEGF may affect endometrial stromal cell survival in an autocrine or paracrine manner. The decrease in FasL level may be due to a stimulation of its degradation. Our results show that FasL in endometrial stromal cells in culture has a cyclic expression model, suggesting that there may be a regulation at the translation level.

Key Words: Key words: apoptosis/chemokines/cytokines/endometrium/growth factors


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