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Mol. Hum. Reprod. Advance Access originally published online on April 8, 2004
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Molecular Human Reproduction, Vol. 10, No. 6, pp. 393-398, 2004
© European Society of Human Reproduction and Embryology 2004

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

M. Berkkanoglu1, O. Guzeloglu-Kayisli1,2, U.A. Kayisli1,3, B.F. Selam1 and A. Arici1,4

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

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

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: apoptosis/chemokines/cytokines/endometrium/growth factors


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