Fas‐Fas Ligand System‐Induced Apoptosis in Human Placenta and Gestational Trophoblastic Disease

Mor, Gil; Gutierrez, Linda S.; Eliza, Mariel; Kahyaoglu, F; Arıcı, Aydın

doi:10.1111/j.1600-0897.1998.tb00396.x

Cited by 109 publications

(30 citation statements)

References 15 publications

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“…Apoptosis of SMCs can be instigated by FasL derived from endothelial cells and monocytes/macrophages, 28,29 and vessel remodeling during atherosclerosis involves SMC apoptosis mediated by Fas/FasL. 30 Expression of FasL by normal trophoblasts has been demonstrated 25,31,32 and a role for the Fas/FasL pathway in the loss of endothelial cells from spiral arteries, 16 as well as in maternal immunotolerance has been defined. 23,24 Our data are further reinforced by the recent finding that a maternal polymorphism leading to decreased Fas expression increased the risk of preeclampsia and pre-eclampsia-associated intrauterine growth restriction in women delivering preterm babies.…”

Section: Discussionmentioning

confidence: 99%

Invasive Trophoblasts Stimulate Vascular Smooth Muscle Cell Apoptosis by a Fas Ligand-Dependent Mechanism

Harris

Keogh

Wareing

et al. 2006

The American Journal of Pathology

138

109

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During pregnancy, trophoblasts migrate from the placenta into uterine spiral arteries, transforming them into wide channels that lack vasoconstrictive properties. In pathological pregnancies, this process is incomplete. To define the fundamental events involved in spiral artery remodeling, we have studied the effect of trophoblasts on vascular smooth muscle cells (SMCs). Here we demonstrate for the first time that apoptosis of SMCs can be initiated by invading trophoblasts. When trophoblasts isolated from normal placenta (primary trophoblasts) or conditioned medium was perfused into spiral or umbilical artery segments, apoptosis of SMCs resulted. Culture of human aortic SMCs (HASMCs) with primary trophoblasts, primary trophoblast-conditioned medium, or a trophoblast-derived cell line (SGHPL-4) also significantly increased SMC apoptosis. Fas is expressed by spiral artery SMCs, and a Fas-activating antibody triggered HASMC apoptosis. Furthermore, a Fas ligand (FasL)-blocking antibody significantly inhibited HASMC apoptosis induced by primary trophoblasts, SGHPL-4, or trophoblast-conditioned medium. Depleting primary trophoblast-conditioned medium of FasL also abrogated SMC apoptosis in vessels in situ. These results suggest that apoptosis triggered by the release of soluble FasL from invading trophoblasts contributes to the loss of smooth muscle from the walls of spiral arteries during pregnancy.

show abstract

Section: Discussionmentioning

confidence: 99%

Invasive Trophoblasts Stimulate Vascular Smooth Muscle Cell Apoptosis by a Fas Ligand-Dependent Mechanism

Harris

Keogh

Wareing

et al. 2006

The American Journal of Pathology

138

109

View full text Add to dashboard Cite

show abstract

“…Indeed, increased concentrations of pro-inflammatory cytokines, such as TNF-a and interleukin (IL)-1 receptor antagonist, have been reported in pre-eclampsia [62][63][64] . Some of these cytokines have been shown to activate apoptotic genes, such as the Fas/FasL system 65,66 and Bcl-2 26 in trophoblast, leading to aberrant placental invasion, function and rejection. In a recent study, we demonstrated that antiinflammatory cytokines (IL-10 and IL-6) increased the resistance of trophoblast cells to Fas-mediated apoptosis, either by inhibiting Fas expression or by inducing Flice Like Inhibitory Protein (Flip) activation.…”

Section: Discussionmentioning

confidence: 99%

Maternal serum of women with pre-eclampsia reduces trophoblast cell viability: evidence for an increased sensitivity to Fas-mediated apoptosis

Neale

Demasio

Illuzi

et al. 2003

The Journal of Maternal-Fetal & Neonatal Medicine

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“…Immunohistochemistry-First and third trimester placental samples were fixed with 4% paraformaldehyde and paraffinembedded as previously described (26). Sections of placenta (5 m) were deparaffinized, rehydrated, and masked with target retrieval solution (Dako, Carpinteria, CA) in a steamer at 95°C for 30 min.…”

Section: Methodsmentioning

confidence: 99%

XAF1 Mediates Tumor Necrosis Factor-α-induced Apoptosis and X-linked Inhibitor of Apoptosis Cleavage by Acting through the Mitochondrial Pathway

Chavez

Visintin

Karassina

et al. 2007

Journal of Biological Chemistry

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Tumor necrosis factor-␣ (TNF-␣) and Fas ligand induce apoptosis by interacting with their corresponding membranebound death receptors and activating caspases. Since both systems share several components of the intracellular apoptotic cascade and are expressed by first trimester trophoblasts, it is unknown how these cells remain resistant to Fas ligand while sensitive to TNF-␣. XAF1 (X-linked inhibitor of apoptosis (XIAP)-associated factor 1) is a proapoptotic protein that antagonizes the caspase-inhibitory activity of XIAP. Here, we demonstrated that XAF1 functions as an alternative pathway for TNF-␣-induced apoptosis by translocating to the mitochondria and promoting XIAP inactivation. In addition, we showed that the overexpression of XAF1 sensitized first trimester trophoblast cells to Fas-mediated apoptosis. Furthermore, we also determined that the differential expression of XAF1 in first and third trimester trophoblast cells was due to changes in XAF1 gene methylation. Our results establish a novel regulatory pathway controlling trophoblast cell survival and provide a molecular mechanism to explain trophoblast sensitivity to TNF-␣ and the increased number of apoptotic trophoblast cells observed near term. Aberrant XAF1 expression and/or localization may have consequences for normal pregnancy outcome.

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Fas‐Fas Ligand System‐Induced Apoptosis in Human Placenta and Gestational Trophoblastic Disease

Abstract: We propose that FasL expression in the placenta is a mechanism responsible for the development of maternal immune tolerance specific for paternal alloantigens and operates in pathologic states characterized by trophoblastic invasion/proliferation.

Cited by 109 publications

References 15 publications

Invasive Trophoblasts Stimulate Vascular Smooth Muscle Cell Apoptosis by a Fas Ligand-Dependent Mechanism

Invasive Trophoblasts Stimulate Vascular Smooth Muscle Cell Apoptosis by a Fas Ligand-Dependent Mechanism

Maternal serum of women with pre-eclampsia reduces trophoblast cell viability: evidence for an increased sensitivity to Fas-mediated apoptosis

XAF1 Mediates Tumor Necrosis Factor-α-induced Apoptosis and X-linked Inhibitor of Apoptosis Cleavage by Acting through the Mitochondrial Pathway

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