Pregnancy‐Specific Glycoproteins Function as Immunomodulators by Inducing Secretion of IL‐10, IL‐6 and TGF‐β1 by Human Monocytes

Snyder, Sara K.; Wessells, Jennifer; Waterhouse, Roseann; Dveksler, Gabriela S.; Wessner, David H.; Wahl, Larry M.; Zimmermann, Wolfgang

doi:10.1111/j.8755-8920.2001.450403.x

Cited by 122 publications

(132 citation statements)

References 33 publications

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“…36 One possible mechanism of IL-6 in preventing miscarriage is modulation of the quality of the Th2 response by increasing the proportion of blocking asymmetric antibodies during implantation and placental vascularization. 62 Although the sensitivity and specificity of the cytokines/receptors in our study are not accurate enough for treatment decisions, a combination of cytokines together with other biomarkers in the future may prove to be useful clinically. Previous studies have shown that TNFreceptors are useful in first-trimester screening of women who are at subsequent risk of preeclampsia.…”

Section: Wwwajogorgmentioning

confidence: 80%

“…Recently, it has been demonstrated that IL-6 is involved in the promotion of Th2 differentiation and the inhibition of Th1 polarization. 62 During the first trimes- Receiver operator characteristics (ROC ) curves for each cytokine and receptor Tumor necrosis factor (TNF )-R2 was shown to be the biomarker that best predicts miscarriage, with an area under the curve of 0.65 (95% confidence interval, 0.47-0.75). A cutoff level of 2202 pg/mL of TNF-R2 gave a sensitivity of 63%, a specificity of 62%, and a positive predictive value of 44% for the prediction of miscarriage.…”

Section: Commentmentioning

confidence: 99%

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Pro- and antiinflammatory cytokines in threatened miscarriages

Calleja‐Agius

Muttukrishna

Pizzey

et al. 2011

American Journal of Obstetrics and Gynecology

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OBJECTIVE:The purpose of this study was to evaluate circulating and intracellular levels of Th1 and Th2 cytokines in women with threatened miscarriage (TM) and subsequent outcome.STUDY DESIGN: Plasma levels of tumor necrosis factor (TNF)-receptors 1 and 2, TNF␣, interferon gamma (IFN␥), and interleukins (IL) -6 and -10 were measured by flow cytometric bead assays in 80 women with TM: 53 women with normal outcome and 27 women who miscarried. Fluorescent antibody labeling was also performed on whole blood in a subgroup of 27 women of TM: 16 women with normal outcome and 11 women who miscarried. RESULTS:Monocyte expression of TNF␣ and circulating levels of TNF␣, IFN␥, IL-10, IL-6, and TNF-R1 were significantly lower, whereas circulating levels of TNF␣/IL-10, IFN␥/IL-10, and TNF␣/IL-6 ratios were significantly higher, in women with TM who subsequently miscarried, compared with the women with normal outcome.CONCLUSION: An increased Th1 type of immune response, which was similar to that observed in preterm delivery, was found in TM cases that were complicated by a subsequent miscarriage.

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Section: Wwwajogorgmentioning

confidence: 80%

Section: Commentmentioning

confidence: 99%

Pro- and antiinflammatory cytokines in threatened miscarriages

Calleja‐Agius

Muttukrishna

Pizzey

et al. 2011

American Journal of Obstetrics and Gynecology

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“…34 In addition, genes involved in renal system processes, neuron development, and cell proliferation (natriuretic peptide precursor b, endothelin1 and 2, bone morphogenic protein, fibroblast growth factor 8) were also down regulated by Fe 2 O 3 but not by MCM-41. Defense response and stress associated genes pregnancy specific beta1 glycoproteins (PSG1 and PSG2) 35 were significantly induced by Fe 2 O 3 while only PSG1 was induced by MCM-41.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Toxicity and Gene Expression Changes Triggered by Oxide Nanoparticles

Dua¹,

Chaudhari²,

Lee³

et al. 2011

Bulletin of the Korean Chemical Society

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Several studies have demonstrated that nanoparticles (NPs) have toxic effects on cultured cell lines, yet there are no clear data describing the overall molecular changes induced by NPs currently in use for human applications. In this study, the in vitro cytotoxicity of three oxide NPs of around 100 nm size, namely, mesoporous silica (MCM-41), iron oxide (Fe 2 O 3 -NPs), and zinc oxide (ZnO-NPs), was evaluated in the human embryonic kidney cell line HEK293. Cell viability assays demonstrated that 100 µg/mL MCM-41, 100 µg/mL Fe 2 O 3 , and 12.5 µg/mL ZnO exhibited 20% reductions in HEK293 cell viability in 24 hrs. DNA microarray analysis was performed on cells treated with these oxide NPs and further validated by real time PCR to understand cytotoxic changes occurring at the molecular level. Microarray analysis of NP-treated cells identified a number of up-and down-regulated genes that were found to be associated with inflammation, stress, and the cell death and defense response. At both the cellular and molecular levels, the toxicity was observed in the following order: ZnO-NPs > Fe 2 O 3 -NPs > MCM-41. In conclusion, our study provides important information regarding the toxicity of these three commonly used oxide NPs, which should be useful in future biomedical applications of these nanoparticles.Key Words : MCM-41, Fe 2 O 3 nanoparticle, ZnO nanoparticle, HEK293, Microarray Introduction Nanoparticles (NPs) have increased surface area to weight ratios relative to the same materials in the non-nano size range. In addition to unusual physical properties, NPs are also more chemically reactive than larger particles, which can be either advantageous or harmful depending on their end use. The nanotech boom started around a decade ago and since then the use of NPs in consumer goods and biomedical applications has dramatically increased. NPs are increasingly applied as drug delivery vehicles, biosensors, imaging contrast reagents, and therapeutic agents. However, it is surprising that even today the scientific and industrial community has no sufficiently clear data on the overall effects of these NPs on human health.NPs are easily internalized into cells 1,2 and some NPs have even been shown to cross the blood brain barrier 3-5 where they alter biological processes and cause toxicity. Various in vitro and in vivo studies indicate that some NPs are associated with serious toxicity issues. The most commonly used in vitro toxicity tests focus on whether potentially toxic agents result in cell death. However, sublethal cellular changes may also exist that are not visible in such toxicity screens, but may significantly affect biological processes at the organismal level. Hence, it is important to identify overall cellular changes mediated by NP exposure. Identification of molecular signatures of toxicity at the genomic or proteomic levels provides comprehensive and reliable high throughput data. These data can then be used to compare, classify, and grade a NP on a scale of toxicity. In the present study we identified the m...

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“…In fact, this glycoprotein is able to suppress the accessory cell-dependent T cell proliferative response, whereas it does not alter the ability of T cells to respond to accessory cell-independent stimuli [15]. Furthermore, murine PSG17 and PSG18 mimic the biological effects of human PSG inducing IL-10, IL-6 and TGF-g expression in human Mo [16], and human PSG1, PSG6 and PSG11 induce the secretion of anti-inflammatory cytokines by human and murine Mo [17]. These findings prompted us to find out whether PSG1a, when released into circulation, may have a role in shifting the T cell immune response to Th2 pathway through the induction of alternative activation of Mo.…”

Section: Introductionmentioning

confidence: 99%

In vivo expression of recombinant pregnancy‐specific glycoprotein 1a induces alternative activation of monocytes and enhances Th2‐type immune response

et al. 2003

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It has been proposed that pregnancy-specific factors could be responsible for shift the balance of cytokine profiles during maternal immune response from Th1-type reactivity into a "less-damaging" Th2-type reactivity. In the present work, we investigated the in vivo function of human pregnancy-specific glycoprotein (PSG)1a, the major variant of PSG polypeptides released into the circulation during pregnancy, on the modulation of the innate and adaptive immune response. For this, BALB/c mice were injected with a vaccinia virus-based vector harboring the human PSG1a cDNA (Vac-PSG1a) 4 days before immunization with ovalbumin (OVA) in complete Freund's adjuvant, and the early specific T cell response against OVA was evaluated 8 days post-immunization. We also studied the activation status of spleen and peritoneal monocytes/macrophages (Mo) populations from Vac-PSG1a-treated mice, and explored whether PSG1a-targeted Mo could affect the Th-type commitment by investigating their impact on the differentiation of naive T cells. Our data show that the treatment with VacPSG1a is able to induce a state of alternative activation on Mo. Furthermore, the generation of the immune response in the context of these alternatively activated antigen-presenting cells may shift T cell differentiation to Th2-type immunity which is more compatible with a successful pregnancy.

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Pregnancy‐Specific Glycoproteins Function as Immunomodulators by Inducing Secretion of IL‐10, IL‐6 and TGF‐β1 by Human Monocytes

Abstract: PSG1, PSG6, PSG6N, and PSG11 induce dose-dependent secretion of anti-inflammatory cytokines by human monocytes. Human and murine PSGs exhibit cross-species activity. Our results are consistent with a role for PSGs in modulation of the innate immune system.

Cited by 122 publications

References 33 publications

Pro- and antiinflammatory cytokines in threatened miscarriages

Pro- and antiinflammatory cytokines in threatened miscarriages

Evaluation of Toxicity and Gene Expression Changes Triggered by Oxide Nanoparticles

In vivo expression of recombinant pregnancy‐specific glycoprotein 1a induces alternative activation of monocytes and enhances Th2‐type immune response

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