Publications by authors named "Carolin Schliefsteiner"

4 Publications

  • Page 1 of 1

Placental Hofbauer Cell Polarization Resists Inflammatory Cues In Vitro.

Int J Mol Sci 2020 Jan 22;21(3). Epub 2020 Jan 22.

Department of Obstetrics and Gynecology, Research Facility, Medical University of Graz, Graz, Austria.

Feto-placental Hofbauer cells (HBCs) are macrophages residing in placental stroma. They are generally described as anti-inflammatory M2 polarized cells, promoting tolerance and tissue remodeling. In certain pathologies, however, a possible phenotypical switch towards pro-inflammatory M1 macrophages has been proposed. The study aimed to determine if HBCs can acquire an M1 phenotype under pro-inflammatory conditions in vitro. HBCs were isolated from healthy human term placentas. Cells were cultivated upon addition of LPS and INF-γ or IL-4 and IL-13 to induce the M1 and M2 phenotype, respectively. Specific cell polarization markers and cytokines, associated with respective phenotypes, were investigated by flow cytometry and ELISA. THP-1 macrophages served as positive control. Pro-inflammatory stimuli reduced M2 markers CD163 and DC-SIGN, but did not induce M1 markers. TNF-α release was increased, but at the same time TGF-β and IL-10 release was upregulated, resembling in part the M2b sub-phenotype. Anti-inflammatory stimuli had no effect on HBC polarization. HBCs maintain their M2 phenotype in vitro despite inflammatory stimuli, which might represent a state of adaption and tolerance to avoid rejection of the semiallogeneic feto-placental unit.
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http://dx.doi.org/10.3390/ijms21030736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038058PMC
January 2020

Sexual dimorphism of miRNA signatures in feto-placental endothelial cells is associated with altered barrier function and actin organization.

Clin Sci (Lond) 2020 01;134(1):39-51

Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.

Endothelial function and the risk for endothelial dysfunction differ between males and females. Besides the action of estrogen, sex chromosome gene expression and programming effects also provoke this sexual dimorphism. MicroRNAs (miRNAs) have emerged as regulators of endothelial cell function and dysfunction. We here hypothesized distinct miRNA expression patterns in male versus female human endothelial cells that contribute to the functional differences. We used our well-established model of fetal endothelial cells isolated from placenta (fpEC) and analyzed sexual dimorphic miRNA expression and potentially affected biological functions. Next-generation miRNA sequencing of fpEC isolated after pregnancies with male and female neonates identified sex-dependent miRNA expression patterns. Potential biological pathways regulated by the altered set of miRNAs were determined using mirPath and mirSystem softwares, and suggested differences in barrier function and actin organization. The identified pathways were further investigated by monolayer impedance measurements (ECIS) and analysis of F-actin organization (Phalloidin). Nine miRNAs were differentially expressed in fpEC of male versus female neonates. Functional pathways most significantly regulated by these miRNAs included 'Adherens junction', 'ECM receptor interaction' and 'Focal adhesion'. These pathways control monolayer barrier function and may be paralleled by altered cytoskeletal organization. In fact, monolayer impedance was higher in fpEC of male progeny, and F-actin staining revealed more pronounced peripheral stress fibers in male versus female fpEC. Our data highlight that endothelial cell function differs between males and females already in utero, and that altered miRNAs are associated with sex dependent differences in barrier function and actin organization.
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http://dx.doi.org/10.1042/CS20190379DOI Listing
January 2020

Maternal Gestational Diabetes Mellitus increases placental and foetal lipoprotein-associated Phospholipase A2 which might exert protective functions against oxidative stress.

Sci Rep 2017 10 3;7(1):12628. Epub 2017 Oct 3.

Department of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria.

Increased Lipoprotein associated phospholipase A (LpPLA) has been associated with inflammatory pathologies, including Type 2 Diabetes. Studies on LpPLA and Gestational Diabetes Mellitus (GDM) are rare, and have focused mostly on maternal outcome. In the present study, we investigated whether LpPLA activity on foetal lipoproteins is altered by maternal GDM and/or obesity (a major risk factor for GDM), thereby contributing to changes in lipoprotein functionality. We identified HDL as the major carrier of LpPLA activity in the foetus, which is in contrast to adults. We observed marked expression of LpPLA in placental macrophages (Hofbauer cells; HBCs) and found that LpPLA activity in these cells was increased by insulin, leptin, and pro-inflammatory cytokines. These regulators were also increased in plasma of children born from GDM pregnancies. Our results suggest that insulin, leptin, and pro-inflammatory cytokines are positive regulators of LpPLA activity in the foeto-placental unit. Of particular interest, functional assays using a specific LpPLA inhibitor suggest that high-density lipoprotein (HDL)-associated LpPLA exerts anti-oxidative, athero-protective functions on placental endothelium and foetus. Our results therefore raise the possibility that foetal HDL-associated LpPLA might act as an anti-inflammatory enzyme improving vascular barrier function.
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http://dx.doi.org/10.1038/s41598-017-13051-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626711PMC
October 2017

Human Placental Hofbauer Cells Maintain an Anti-inflammatory M2 Phenotype despite the Presence of Gestational Diabetes Mellitus.

Front Immunol 2017 31;8:888. Epub 2017 Jul 31.

Perinatal Research Laboratory, Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.

Background: Hofbauer cells (HBCs) are macrophages of the feto-placental unit. Despite the general view that these cells have an anti-inflammatory M2 phenotype, recent studies have claimed that pregnancy pathologies-e.g., gestational diabetes mellitus (GDM)-cause a switch from an M2 to an M1 pro-inflammatory phenotype in HBCs. The pilot-study presented here challenges this claim, showing that HBCs maintain anti-inflammatory properties in spite of the hyperglycemic, low-grade inflammatory environment of GDM.

Methods: HBCs were isolated from placentae of healthy women ( = 5) and women with GDM ( = 6) diagnosed in the second trimester. FACS was used to measure surface markers associated with either M1 or M2 phenotype on the cells. In addition, placental tissue sections were subjected to immune histochemical imaging to assess the phenotype within the tissue context. Supernatant from control and GDM HBCs was collected at defined time points and used in a multiplex ELISA-on-beads approach to assess secretion of cytokines, chemokines, and growth factors. The effect of HBC cell culture supernatant on placental endothelial activation was investigated.

Results: FACS and immune staining showed that, indeed, M2 markers, such as CD206 and CD209, are increased in HBCs isolated from GDM placentae. Also, the M1 marker CD86 was increased, but only by trend. Secretion of numerous cytokines, chemokines and growth factors was not changed; pro-inflammatory interleukin (IL)-1β and IL-6 release form GDM HBC was increased but not significant. Exposure to GDM HBC supernatant did not induce cell adhesion molecules (VCAM-1, selectins, vascular endothelial-cadherin) in placental endothelial cells compared to supernatant from control HBCs, an induction of intracellular adhesion molecule 1 was observed however.

Conclusion: Our study-although performed in a small set of patients-shows that placental macrophages maintain their anti-inflammatory, tissue remodeling M2 phenotype even in pregnancies affected by gestational diabetes. This consistent phenotype might be important for propagation of maternal tolerance toward the fetus and for protection of the fetus from a low-grade inflammatory environment.
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http://dx.doi.org/10.3389/fimmu.2017.00888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534476PMC
July 2017
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