Cytokine Release From Placental Endothelial Cells, a Process Associated With Preterm Labour in the Absence of Intrauterine Infection

Steinborn, Andrea; Niederhut, A.; Solbach, Christine; Hildenbrand, Ralf; Sohn, Cheol Ho; Kaufmann, M.

doi:10.1006/cyto.1998.0399

Cited by 55 publications

(25 citation statements)

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“…However, we found no differences in serum sFasL concentrations between treated and untreated women with severe preeclampsia, making it less likely that exogenous steroids influenced our results. Although physiologic factors, such as prolonged labor or duration of ruptured membranes, are associated with cytokine release (41), which could potentially affect Fas expression, we found no overall differences between groups with respect to these measurements. Indeed, many of the women with severe preeclampsia were delivered of their infants in the absence of labor, with intact membranes.…”

Section: Discussioncontrasting

confidence: 68%

Fas and Fas Ligand Expression in Maternal Blood and in Umbilical Cord Blood in Preeclampsia

et al. 2001

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The Fas-Fas ligand (FasL) pathway of apoptosis is abnormally activated in diseases associated with impaired immune tolerance or chronic inflammation. Pregnancy-related hypertension is a spectrum of disease that commonly causes significant morbidity in women and in their newborn infants, is associated with generalized inflammation, and may be causally related to impaired maternal-fetal tolerance. Our recent observation of enhanced trophoblast expression of FasL in one form of pregnancy-related hypertension led us to hypothesize that this group of disorders might be associated with abnormal activation of the Fas-FasL pathway. To test this hypothesis, we prospectively quantified soluble and leukocyte-associated Fas receptor and FasL in the maternal and umbilical cord blood (CB) sera of 20 gestations complicated by preeclampsia and of 18 normal control gestations, using ELISA and flow cytometric analyses. We determined higher soluble FasL levels in paired maternal and CB sera of hypertensive gestations compared with control gestations (p Ͻ 0.01); in contrast, soluble Fas levels were similar between groups. Surface expression of FasL was lower on maternal (p Ͻ 0.01) and CB (p Ͻ 0.05) neutrophils from affected gestations, whereas surface Fas expression was lower on maternal (p Ͻ 0.02), but not CB, neutrophils and lymphocytes. We conclude that expression of Fas and FasL in sera and on leukocytes is altered in gestations complicated by preeclampsia, and speculate that activation of the Fas-FasL pathway mediates associated pathologic processes in affected women and in their neonates. Activation of the Fas-Fas Ligand pathway involves cellular interactions between the Fas receptor and FasL, and can result in apoptosis or in an inflammatory response (1). The Fas receptor (CD95, Apo-1, FasR), a type I integral membrane protein belonging to the tumor necrosis factor receptor family, is expressed on numerous cell types including hematopoietic cells, and its expression increases during inflammation (1). In contrast, expression of FasL (CD95L), a type II transmembrane molecule belonging to the tumor necrosis factor receptor superfamily, is limited to certain leukocytes and tissues with immune privilege (2). Fas-FasL interactions leading to clonal deletion of antigen-presenting cells have been implicated in the establishment of graft tolerance (3), and provide one explanation for the immune privilege status of certain tissues, including the placenta, cornea, and testis (2). In contrast, abnormal function of the Fas-FasL pathway is involved in the pathogenesis of a variety of disorders, including cytopenias, autoimmune diseases, graft-versus-host disease, and graft rejection (1,(3)(4)(5)(6).Mice with the gld mutation are deficient in FasL function and have smaller litters with decreased viability (7). Studies in these mice suggest that the Fas-FasL pathway contributes to preservation of the fetal allograft by preventing the trafficking of activated leukocytes between the mother and fetus during normal gestation, observations also ...

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Section: Discussioncontrasting

confidence: 68%

Fas and Fas Ligand Expression in Maternal Blood and in Umbilical Cord Blood in Preeclampsia

et al. 2001

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“…Conditions such as placental insufficiency/fetal growth restriction, preeclampsia, and gestational diabetes are relatively common pregnancy disorders in which elevated cytokine concentrations are believed to play a role (Hamai et al, 1997;Steinborn et al, 1999;Saji et al, 2000;Johnson et al, 2002). Placental expression of the proinflammatory cytokine tumor necrosis factor-␣ (TNF-␣) is elevated in preeclampsia and gestational diabetes (Hamai et al, 1997;Coughlan et al, 2001;Kirwan et al, 2002).…”

mentioning

confidence: 99%

Independent Regulation of Apical and Basolateral Drug Transporter Expression and Function in Placental Trophoblasts by Cytokines, Steroids, and Growth Factors

Evseenko

Paxton²,

Keelan³

2007

Drug Metab Dispos

166

135

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ABSTRACT:Placental ATP binding cassette (ABC) transporters protect placental and fetal tissues by effluxing xenobiotics and endogenous metabolites. We have investigated the effects of cytokines and survival/growth factors, implicated in various placental pathologies, on ABC transporter expression and function in primary placental trophoblast cells. Treatment of primary term trophoblasts in vitro with tumor necrosis factor-␣ (TNF-␣) or interleukin (IL)-1␤ decreased mRNA and protein expression of apical transporters ABCB1/multidrug resistance gene product 1 (MDR1) and ABCG2/ breast cancer resistance protein (BCRP) protein by 40 to 50% (P < 0.05). In contrast, IL-6 increased mRNA and protein expression of the basolateral transporter ABCB4/MDR3 (P < 0.05), whereas ABCC1/MRP1 expression was unaltered. Pretreatment of trophoblasts with TNF-␣ over 48 h resulted in significantly decreased BCRP efflux activity (increased mitoxantrone accumulation) with minimal changes in MDR1/3 activity. Epidermal growth factor (EGF) and insulin-like growth factor II, on the other hand, significantly increased BCRP expression at the mRNA and protein level (P < 0.05); EGF treatment also increased BCRP functional activity. Estradiol stimulated BCRP, MDR1, and MDR3 mRNA and protein expression by 40 to 60% and increased MDR1/3 functional activity (P < 0.05). Progesterone had modest positive effects on MRP1 mRNA and MDR1 protein expression (P < 0.05). In conclusion, this study shows that proinflammatory cytokines, sex steroids, and growth factors exert independent effects on expression of apical and basolateral placental ABC transporters in primary trophoblast. Such changes could alter placental drug disposition, increase fetal susceptibility to toxic xenobiotics, and impact on placental viability and function.

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Section: Discussionmentioning

confidence: 97%

“…In the case of preterm delivery without chorioamnionitis, they found an intense IL-6 and IL-1ß immunoreactivity in fetal endothelial cells within trophoblastic villi [26]. In contrast, only a poor IL-6 and IL-1ß immunoreactivity has been detected in endothelial cells within villi obtained from infected preterm delivering women [26]. In addition, it has been demonstrated that the elevated placental IL-6 and IL-1ß production of placental cell cultures is associated with uncontrolled preterm labor and not due to intra-amniotic infection; in comparison to these results, placental tissue cultures obtained from women with histologically confirmed chorioamnionitis have produced significantly smaller amounts of these cytokines [27].…”

Section: Discussionmentioning

confidence: 97%

“…Steinborn et al [26] have investigated the localization of IL-6, IL-1ß, and TNF-· immunoreactivity within trophoblastic villi and fetal membranes by using immunohistochemical analysis. In the case of preterm delivery without chorioamnionitis, they found an intense IL-6 and IL-1ß immunoreactivity in fetal endothelial cells within trophoblastic villi [26].…”

Section: Discussionmentioning

confidence: 99%

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Increased Levels of Interleukin-6 in Cervical Secretions and Assessment of the Uterine Cervix by Transvaginal Ultrasonography Predict Preterm Premature Rupture of the Membranes

et al. 2003

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Objective: The objective of this study was to investigate the predictive factors of premature rupture of the membranes (preterm PROM). Methods: The study was undertaken with cervical secretions collected from 72 consenting singleton pregnant women between 20 and 33 weeks of gestation. The levels of interleukin (IL) 1α, IL-1β, IL-6, IL-8, matrix metalloproteinase (MMP) 1, MMP-2, MMP-9, tissue inhibitors of matrix metalloproteinase (TIMP) 1, TIMP-2, granulocyte elastase, and fetal fibronectin in cervical diluted specimens were measured by immunoassay, and the uterine cervix was assessed by transvaginal ultrasonography. Demographic, obstetric, clinical, neonatal, and laboratory data were analyzed by univariate analysis, multiple logistic regression, and receiver operator characteristic curve analysis. Results: Preterm PROM occurred in 6 women, and 63 women delivered at term. Multiple logistic regression analysis indicated a significant independent association with preterm PROM for the cervical IL-6 levels and cervical length. The receiver operator characteristic curve analysis revealed that an IL-6 level of ≧240 pg/ml in cervical secretions and a cervical length of ≤28 mm had higher diagnostic performance in predicting preterm PROM. Conclusion: It is suggested that preterm PROM is associated with increased cervical IL-6 levels and a short cervix.

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Cytokine Release From Placental Endothelial Cells, a Process Associated With Preterm Labour in the Absence of Intrauterine Infection

Cited by 55 publications

References 0 publications

Fas and Fas Ligand Expression in Maternal Blood and in Umbilical Cord Blood in Preeclampsia

Fas and Fas Ligand Expression in Maternal Blood and in Umbilical Cord Blood in Preeclampsia

Independent Regulation of Apical and Basolateral Drug Transporter Expression and Function in Placental Trophoblasts by Cytokines, Steroids, and Growth Factors

Increased Levels of Interleukin-6 in Cervical Secretions and Assessment of the Uterine Cervix by Transvaginal Ultrasonography Predict Preterm Premature Rupture of the Membranes

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